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Autologous chimeric antigen receptor (CAR)-modified T (CAR-T) cell therapy has displayed high efficacy in the treatment of hematological malignancies. Up to now, 11 autologous CAR-T cell products have been approved for the management of malignancies globally. However, the application of autologous CAR-T cell therapy has many individual limitations, long time-consuming, highly cost, and the risk of manufacturing failure. Indeed, some patients would not benefit from autologous CAR-T cell products because of rapid disease progression. Allogeneic CAR-T cells especially universal CAR-T (U-CAR-T) cell therapy are superior to these challenges of autologous CAR-T cells. In this review, we describe basic study and clinical trials of U-CAR-T cell therapeutic methods for malignancies. In addition, we summarize the problems encountered and potential solutions.

Colorectal cancer (CRC) is a major contributor to global cancer incidence and mortality. Conventional treatments have limitations; hence, innovative approaches are imperative. Recent advancements in cancer research have led to the development of personalized targeted therapies and immunotherapies. Immunotherapy, in particular, T cell-based therapies, exhibited to be promising in enhancing cancer treatment outcomes. This review focuses on the landscape of engineered T cells as a potential option for the treatment of CRC. It highlights the approaches, challenges and current advancements in this field. As the understanding of molecular mechanisms increases, engineered T cells hold great potential in revolutionizing cancer treatment. To fully explore their safety efficacy in improving patient outcomes, further research and clinical trials are necessary.

Aim: The aim was to evaluate the efficacy and safety of chimeric antigen receptor T (CAR-T) cell in B-cell non-Hodgkin lymphoma (B-NHL). Materials & methods: A meta-analysis was conducted using eligible clinical trials, which were obtained from electronic medical literature databases. Results: A total of 24 clinical trials with 590 patients were included. The best overall response rate was 66% and complete remission rate was 46%. The incidence rates of cytokine-release syndrome and neurotoxicity (grade ≥ 3) were 9 and 5%, respectively. The various clinical factors were analyzed. Autogenic CAR-T cell may lead to improved efficacy than allogeneic CAR-T cell. CD20 CAR-T cell may show increased efficacy than CD19 CAR-T cell. Conclusion: CAR-T immunotherapy has remarkable efficacy and low toxicity in relapsed/refractory B-NHL.

Despite the success of antiretroviral therapy in suppressing HIV to an undetectable level in the blood and improving patients' quality of life, HIV persists in antiretroviral therapy-treated patients and threatens their lives. Anti-HIV chimeric antigen receptor (CAR) T cells could offer a cure by recognizing and killing virus-producing cells in an Env-specific manner. In this review, the authors summarize several important aspects of the development of anti-HIV CAR T cells, with a special focus on the evolution of CAR design for enhanced potency and targeting specificity, and also outline the challenges that still need to be addressed to take anti-HIV CAR T cells from a hopeful approach to a real HIV cure.

Aim: Peritoneal metastasis is often present in end-stage neoplastic diseases, including recurrent colorectal cancer and is associated with decreased overall survival. Novel methods are needed. Materials & methods: We constructed first-, second- and third-generation chimeric antigen receptors (CARs) specific for NKG2D ligands and modified human T cells with mRNA electroporation. Results: NKG2D CAR expression was detectable for at least 6 days postelectroporation and mediated efficient cytotoxicity against NKG2DL+ tumor cells, but not NKG2DL-cells. Multiple infusions of the first-generation CAR-T cells into immunodeficient mice bearing established peritoneal colorectal xenografts led to significantly reduced tumor burden. Conclusion: mRNA CAR is an economical way to test new CARs and potentiates controlling on-target/off-tumor toxicity and cytokine storms. The use of NKG2D RNA CARs to treat colorectal peritoneal metastasis warrants further investigation.

Recent therapeutic advances in cancer treatment recruit immune system potentiation against malignant cells. Numerous ongoing clinical trials on immunotherapy methods, either monotherapy or combination therapy, are investigating the impeding factors on the way of acute myeloid leukemia (AML) treatment. Due to the genetic diversity in AML progenitors, combining various strategies is more likely to be useful for improving patient outcomes. This review describes the details of applying monoclonal antibodies against AML, focusing on CD33, CD123, FLT3, CD45 and CD66 targeting. Furthermore, it clarifies the importance of immunotoxins, bispecific antibodies, chimeric antigen receptor (CAR)-T cells and T cell receptor-modified cells as reinforcing agents for monoclonal antibodies.

The chimeric antigen receptor T (CAR-T) cells play an antileukemia role, and can be used to treat or prevent relapse by targeting minimal residual disease for patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the infusion of allogeneic CAR-T cells may also cause graft-versus-host disease, which limited their applications during and after allo-HSCT. In this review, we discuss the clinical trials that applying CAR-T cells before allo-HSCT and the use of donor-derived CAR-T cells as conditioning regimen during allo-HSCT. At last, we analyzed the effect of donor-derived CAR-T cells on preventive infusion after allo-HSCT.

Despite recent advancements in therapeutic options for advanced hepatobiliary cancers, there remains an unmet need for innovative systemic treatments. Immunotherapy has shown an ability to provide prolonged clinical benefit, but this benefit remains limited to a small subset of patients. Numerous ongoing endeavors are investigating novel immunotherapy concepts. Immunotherapies that have demonstrated clinical efficacy in hepatobiliary cancers include PD-1 inhibitor therapy and CTLA-4 inhibitor therapy. Novel immunotherapy concepts include targeting emerging checkpoint proteins, bispecific T-cell engagers, combinatorial trials with checkpoint inhibitors, oncolytic virotherapy and chimeric antigen receptor T cells. The goal for these new treatment strategies is to achieve a meaningful expansion of patients deriving prolonged clinical benefit from immunotherapy.

Artificially boosting body's immune response is one of the most exciting, effective and promising advancements in the treatment of cancers. Cancer immunotherapeutics consist of variety of treatment approaches such as cytokine therapy, adoptive T-cell transfer therapy, and antibodies that stimulate innate and adoptive immune responses. In addition to this, development of HPV vaccine has paved way toward the development of other cancer vaccines. Checkpoint blockade inhibitors, for example, anti-programmed cell death protein 1 and anti-cytotoxic T-lymphocyte-associated antigen-4, chimeric antigen receptor T-cell therapy and monoclonal antibodies are emerging as other major breakthroughs that are highly effective against cancer. This review addresses the current status of immunotherapeutic strategies against cancer and provides baseline data for future research.

Adoptive T-lymphocyte transfer-based immunotherapy for cancers has seen huge leaps with both CARs and engineered TCRs. Despite this, issues relating to safety and efficacy persist. To address this, chimeric switch receptors have been created to reverse the outcomes of their original signaling pathways in order to confer immune cells with the ability to overcome the immunosuppressive tumor microenvironment and to allow them to have greater in vivo persistence. Activating switch receptors exploit the inhibitory molecules expressed by cancer cells to further stimulate the tumor antigen-specific T lymphocytes. On the other hand, inhibitory switch receptors inhibit the effects of tumor-reactive T lymphocytes on unintended targets. This paper reviews the switch receptors reported thus far, and lists out potential improvements and future works.

Treatment of patients with relapsed or refractory lymphoma may require allogenic hematopoietic stem cell transplant (HSCT), but treatment of post-transplant relapse disease remains very challenging. Donor lymphocyte infusion and blinatumomab have been used with limited success for the treatment of relapse. Initial data on donor-derived CAR T cells has shown this modality to be safe and highly effective in various hematological malignancies. We present a case of a patient with highly refractory, transformed follicular lymphoma who failed both autologous and allogenic HSCT. Patient achieved long-lasting complete remission with the use of donor origin CD19 CAR T-cell therapy, without any evidence of graft-versus-host disease flare. Our patient later developed disseminated coccidioidomycosis and persistent hypogammaglobulinemia. Immunotherapy using CD19 CAR T cells can be a highly effective salvage modality, especially in cases of focal lymphoma relapse. Long-term immunosuppression secondary to B cell lymphopenia, hypogammaglobulinemia, immunoglobulin subclass deficiency, fungal infections and other infectious complications need to be monitored and promptly treated as indicated.

Relapsed/refractory acute lymphoblastic leukemia (ALL) has a low remission rate after chemotherapy, a high relapse rate and poor long-term survival even when allogeneic hematopoietic stem cell transplantation (allo-HSCT) is performed. Chimeric antigen receptors redirected T cells (CAR-T cells) can enhance disease remission with a favorable outcome for relapsed/refractory ALL, though some cases quickly relapsed after CAR-T cell treatment. Thus, treatment with CAR-T cells followed by allo-HSCT may be the best way to treat relapsed/refractory ALL. In this review, we first discuss the different types of CAR-T cells. We then discuss the treatment of relapsed/refractory ALL using only CAR-T cells. Finally, we discuss the use of CAR-T cells, followed by allo-HSCT, for the treatment of relapsed/refractory ALL.

Due to the critical role of T cells in the immune surveillance of ovarian cancer, adoptive T-cell therapies are receiving increased attention as an immunotherapeutic approach for ovarian cancer. Chimeric antigen receptors (CARs), constructed by incorporating the single-chain Fv fragment to a T-cell signaling domain such as CD3 ζ or Fc receptor γ chain, endow T cell with nonmajor histocompatibility complex-restricted specificity. Dual specificity, trans-signaling CARs and affinity-tuned single-chain Fv fragment have broadened the applicability of CAR-engineered T-cell therapy and may be considered preferential to T cell receptor T-cell therapy in clinical care. As new insights into the CAR-engineered T cells have emerged over the last decade, we review the development of CAR T-cell therapy and discuss the progress and safety concerns regarding its translation from basic research into clinical care of ovarian cancer.

The remarkable clinical outcomes of the treatment for B-cell malignancies through the application of CD19 chimeric antigen receptor T (CAR-T) cells have made adoptive immunotherapy with genetically modified immune effector cells a hotspot in the field of antitumor. However, numerous toxicities of CAR-T cells have been identified. Thus, some studies have resorted to another cytotoxic cell, NK-92 cell, to reach for better efficacy with minimal toxicity. Preclinical studies have confirmed the safety and feasibility of the genetically modified NK-92 cells with highly specific cytotoxicity in vitro and in vivo. Therefore, it is expected that NK-92 cell becomes another ideal carrier for CAR for its unique advantages over primary NK cells, parental NK-92 cells and autologous T cells.

One obstacle to the application of immunotherapy to solid malignancies is to overcome the existing tolerance to self-antigens. Vaccine strategies aimed at harnessing endogenous antitumor T cells are limited by the T-cell receptor repertoire, which can be detected within the thymus as central tolerance or rendered nonfunctional by post-thymic mechanisms of peripheral tolerance. Adoptive immunotherapy can overcome these obstacles, since therapeutically effective T cells can be engineered to recognize tumors. Continued advancements in novel treatments, including immunotherapy, in solid malignancies are imperative. While mesothelin is an attractive target for cancer immunotherapy given its normal expression is limited to mesothelial cells, the breakthrough for chimeric antigen receptor T-cell treatment against this antigen is still forthcoming.

Chimeric antigen receptor (CAR) T-cell therapy has recently been recommended for approval for certain B-cell malignancies bringing the approach closer to mainstream cancer treatment. This rapid rise to prominence has been driven by impressive clinical results and the means to successfully commercialize the approach now being actively pursued. The current success of CAR T cells in B-cell malignancies relies upon the absolute lineage specificity of the CD19 antigen. CARs can also be targeted using non-antibody approaches, including the use of receptors and ligands to provide target specificity that have different specificities and binding kinetics. The specific examples of NKG2D and Erb-B are used that provide different characteristics and target profiles for CAR T-cell therapy of cancer.

Chimeric antigen receptor T-cell therapy has achieved highly promising results in clinical trials, particularly in B-cell malignancies. However, reports of serious adverse events including a number of patient deaths have raised concerns about safety of this treatment. Presently available preclinical models are not designed for predicting toxicities seen in human patients. Besides choosing the right animal model, careful considerations must be taken in chimeric antigen receptor T-cell design and the amount of T cells infused. The development of more sophisticated in vitro models and humanized mouse models for preclinical modeling and toxicity tests will help us to improve the design of clinical trials in cancer immunotherapy.

The clinical success of checkpoint inhibitors has led to a renaissance of interest in cancer immunotherapies. In particular, the possibility of ex vivo expanding autologous lymphocytes that specifically recognize tumor cells has attracted much research and clinical trial interest. In this review, we discuss the historical background of tumor immunotherapy using cell-based approaches, and provide some rationale for overcoming current barriers to success of autologous immunotherapy. An overview of adoptive transfer of lymphocytes, tumor infiltrating lymphocytes and dendritic cell therapies is provided. We conclude with discussing the possibility of gene-manipulating immune cells in order to augment therapeutic activity, including silencing of the immune-suppressive zinc finger orphan nuclear receptor, NR2F6, as an attractive means of overcoming tumor-associated immune suppression.

Non-small cell lung cancer (NSCLC) is still the leading cause of cancer death worldwide, with a poor prognosis. In the era of immunotherapies, the field is rapidly changing, and the clinician needs to be aware of the current state and future perspectives of immunotherapeutic strategies. In this review, we discuss the current status of immune checkpoint inhibitors, cancer vaccines and cellular therapies specifically in NSCLC. Last but not least, we will discuss rational combination strategies that are promising for the near future.

Immunotherapy with chimeric antigen receptor (CAR) T cells has been advancing steadily in clinical trials. Since the ability of engineered T cells to recognize intended tumor-associated targets is crucial for the therapeutic success, antigen-binding domains play an important role in shaping T-cell responses. Single-chain antibody and T-cell receptor fragments, natural ligands, repeat proteins, combinations of the above and universal tag-specific domains have all been used in the antigen-binding moiety of chimeric receptors. Here we outline the advantages and disadvantages of different domains, discuss the concepts of affinity and specificity, and highlight the recent progress of each targeting strategy.

CD19, CD20 chimeric antigen receptor T (CAR T) cell therapy has shown promising results for the treatment of relapsed or refractory hematological malignancies. Best results have been reported in acute lymphoblastic leukemia patients with a complete response rate above 80%. Patients who received donor-derived CAR T cells for the relapsed malignancy after stem cell transplantation (allogenic hematopoietic stem cell transplant) were identified from the published trials. A total of 72 patients from seven studies were treated with donor-derived CAR T cells. Only five out of 72 patients (6.9%) developed graft versus host disease. Use of donor-derived CAR T cell for relapse prophylaxis, minimal residual disease clearance or salvage from relapse is therefore highly effective, and risk of graft versus host disease flare is very low. Side effects include cytokine release syndrome, tumor lysis syndrome, B-cell aplasia along with CNS toxicity.

Patients with glioblastoma have a very poor prognosis. Adoptive cellular therapy (ACT) is defined as the collection of circulating or tumor-infiltrating lymphocytes, their selection, modification, expansion and activation, and their re-administration to patients in order to induce antitumor activity. Although various ACTs have been attempted, most failed to improve the outcome. Immune checkpoint blockade antibodies and T cell engineering with tumor-specific chimeric antigen receptors suggest the emergence of a new era of immunotherapy. Here, we summarize approaches with ACTs using genetically modified T cells, which have been improved by enhancing their antitumor activity, and discuss strategies to develop these therapies. The mechanisms by which gliomas modulate and evade the immune system are also discussed.

Synovial sarcoma is a rare soft tissue sarcoma characterized by a t(X;18) translocation, which results in a SYT-SSX gene fusion. In the metastatic setting, chemotherapy has limited, durable efficacy prompting the necessity for new therapeutic modalities. One emerging new strategy involves T-cell-directed therapy such as tumor-infiltrating lymphocytes or the development of T cells that are genetically engineered to express a T-cell receptor against a cancer testis antigen. Of these approaches, engineered T cells that recognize NY-ESO-1 are the furthest along in development. Completed and on-going clinical trials have shown promise and there are efforts to continue to optimize the current approach.

Aim: To systemically evaluate the efficacy and safety of adoptive cellular therapy for the treatment of gastric cancer (GC)., Materials & Methods: We performed a systemic review and meta-analysis of nine eligible trials with GC and evaluated the effect of adoptive cellular therapy on the overall survival (OS) rate, T-cell subsets and adverse events., Results: Overall, 829 patients were involved in the analysis. Adoptive cellular therapy significantly improved the OS rate compared with the control group. Meanwhile, we observed greatly increased percentages of CD3(+), CD4(+) and CD4(+)/CD8(+) in cellular therapy groups., Conclusion: Adoptive cellular therapy combined with adjuvant therapy resulted in significantly better OS rates, progression-free survival and T-lymphocyte responses in patients with GC.

One of the strategies to enhance immune response against tumors has been the use of vaccines against tumor-associated antigens (TAAs). MUC1 is a TAA that is overexpressed in many malignancies being linked to worse prognosis. Moreover, tumor MUC1 is hypoglycosylated revealing new epitopes that are antigenic and potential T-cell targets. TG4010 is a recombinant viral vaccine targeting MUC1, also encoding for IL-2. TG4010 has been tested in Phase I-II trials demonstrating a consistent safety profile with mild local reactions as main side effect. These studies have confirmed immune responses to the vaccine product. Clinical efficacy has been observed mainly in patients with non-small-cell lung cancer in combination with chemotherapy. Peripheral activated NK cells are currently being validated as biomarkers of response.

The clinical management of bladder cancer has not changed significantly in several decades. In particular, intravesical bacillus Calmette-Guérin (BCG) immunotherapy has been a mainstay for high-risk nonmuscle invasive bladder cancer since the late 1970s/early 1980s. This is despite the fact that bladder cancer has the highest recurrence rates of any cancer and BCG immunotherapy has not been shown to induce a tumor-specific immune response. We and others have hypothesized that immunotherapies capable of inducing tumor-specific adaptive immunity are needed to impact bladder cancer morbidity and mortality. This article summarizes the preclinical and clinical development of bladder cancer immunotherapies with an emphasis on the last 5 years. Expected progress in the near future is also discussed.

Mesothelin is a promising target for immune-based therapy, specifically for mesothelioma and pancreatic and ovarian cancers that have high levels of mesothelin expression. Many preclinical and clinical studies that target tumors with high mesothelin expression with antibodies, immunotoxins, antibody-drug conjugates and vaccines have shown the potential of mesothelin as a target. Studies of T cells genetically modified with chimeric antigen receptors (CAR) report significant efficacy in hematologic malignancies, and antimesothelin CAR T cells are currently being investigated in clinical studies. Here we outline the rationale for using mesothelin as a target for immunotherapy, review the clinical and preclinical studies evaluating mesothelin-directed therapies and explore the promise of CAR T cells directed against mesothelin for immunotherapy in the future.

Chimeric antigen receptor (CAR) T-cell therapy has recently come into the spotlight due to impressive results in patients with B-cell acute lymphoblastic leukemia. By targeting CD19, a marker expressed most B-cell tumors, as well as normal B cells, CAR T-cell therapy has been investigated as a treatment strategy for B-cell leukemia and lymphoma. This review will discuss the successes of this therapy for the treatment of B-cell acute lymphoblastic leukemia and the challenges to this therapeutic strategy. We will also discuss application of CAR T-cell therapy to chronic lymphocytic leukemia and other B-cell malignancies including a follicular lymphoma, diffuse large B-cell lymphoma, as well as acute and plasma cell malignancies.

Adoptive transfer of T cells specific for viral pathogens offers an attractive method for hastening immune reconstitution and protective immunity in patients following stem cell transplantation. The largest experience to date has been in the context of treatment or prevention of cytomegalovirus or Epstein-Barr virus. A number of technical hurdles have now been overcome allowing consideration of more widespread application of products compliant with Good Manufacturing Practice regulations, and of the development of commercialization pathways for these products. This review summarizes progress to date and highlights some of the areas that remain problematic and that require further innovation and evaluation before more widespread adoption is considered.

Cancer immune therapy, in particular the use of checkpoint inhibitors and adoptive transfer of T cells has recently demonstrated significant clinical responses against several tumor types. Unfortunately, these therapies are frequently accompanied by severe toxicities, underscoring the need for markers that provide information on therapy response. Monitoring immune responses in the tumor microenvironment and peripheral blood prior to and during these therapies will provide better insight into the mechanisms underlying clinical activities, and will potentially enable the identification of such markers. In this review, we present an overview of adoptive T-cell trials conducted with a special focus on immune monitoring, and argue that accurate monitoring of T cells is pivotal to further development of immune therapies to treat cancer.

Background: Donor lymphocyte infusion is not feasible in recipients of cord blood transplantation., Aim: We investigated whether infusion of T cells expanded from cord blood is effective in the treatment of model mice of Epstein-Barr virus (EBV)-associated lymphoproliferative disease (LPD)., Materials & Methods: Humanized mice with reconstituted human immune system were prepared and LPD was induced by inoculating EBV intravenously. T cells were expanded from the same sample of cord blood as used for generation of humanized mice and infused to EBV-infected humanized mice., Results: Mice treated with expanded cord blood T cells lived significantly longer than control mice (p = 0.036)., Conclusion: Infusion of T cells expanded from cord blood was effective in the treatment of model mice for EBV-associated LPD.

Radiation therapy controls local disease but also prompts the release of tumor-associated antigens and stress-related danger signals that primes T cells to promote tumor regression at unirradiated sites known as the abscopal effect. This may be enhanced by blocking inhibitory immune signals that modulate immune activity through a variety of mechanisms. Indeed, abscopal responses have occurred in patients with lung cancer or melanoma when given anti-CTLA4 antibody and radiation. Other approaches involve expanding and reinfusing T or NK cells or engineered T cells to express receptors that target specific tumor peptides. These approaches may be useful for immunocompromised patients receiving radiation. Preclinical and clinical studies are testing both immune checkpoint-based strategies and adoptive immunotherapies with radiation.

Recent spectacular success in the adoptive cell therapy of leukemia and lymphoma with chimeric antigen receptor (CAR)-modified T cells raised the expectations that this therapy may be efficacious in a wide range of cancer entities. The expectations are based on the predefined specificity of CAR T cells by an antibody-derived binding domain that acts independently of the natural T-cell receptor, recognizes targets independently of presentation by the major histocompatibility complex and allows targeting toward virtually any cell surface antigen. We here discuss that targeting CAR T cells toward solid tumors faces certain circumstances critical for the therapeutic success. Targeting tumor stroma and taking advantage of TRUCK cells, in other words, CAR T cells with inducible release of a transgenic payload, are some strategies envisaged to overcome current limitations in the near future.

Chimeric antigen receptor (CAR) based immunotherapy has been under development for the last 25 years and is now a promising new treatment modality in the field of cancer immunotherapy. The approach involves genetically engineering T cells to target malignant cells through expression of a bespoke fusion receptor that couples an HLA-independent antigen recognition domain to one or more intracellular T-cell activating modules. Multiple clinical trials are now underway in several centers to investigate CAR T-cell immunotherapy of diverse hematologic and solid tumor types. The most successful results have been achieved in the treatment of patients with B-cell malignancies, in whom several complete and durable responses have been achieved. This review focuses on the preclinical and clinical development of CAR T-cell immunotherapy of solid cancers, targeted against members of the ErbB family.

Chimeric antigen receptor (CAR) T cells form part of a broad wave of immunotherapies that are showing promise in early phase cancer clinical trials. This clinical delivery has been based upon preclinical efficacy testing that confirmed the proof of principle of the therapy. However, CAR T-cell therapy does not exist alone as T cells are generally given in combination with patient preconditioning, most commonly in the form of chemotherapy, and may also include systemic cytokine support, both of which are associated with toxicity. Consequently, complete CAR T-cell therapy includes elements where the toxicity profile is well known, but also includes the CAR T cell itself, for which toxicity profiles are largely unknown. With recent reports of adverse events associated with CAR T-cell therapy, there is now concern that current preclinical models may not be fit for purpose with respect to CAR T-cell toxicity profiling. Here, we explore the preclinical models used to validate CAR T-cell function and examine their potential to predict CAR T-cell driven toxicities for the future.

Adoptive immunotherapy with tumor-reactive autologous T cells, either expanded from tumor specimens or genetically engineered to express tumor-reactive T-cell receptors and chimeric antigen receptors, is holding promising results in clinical trials. Several critical issues have been identified and results underline the possibility to exploit cytokines to further ameliorate the efficacy of current treatment protocols, also encompassing adoptive T-cell therapy. Here we review latest developments on the use of cytokines to better direct the nature of the T-cell infusion product, T-cell function and persistence in vivo, as well as to modulate the tumor microenvironment.

Novel effective immunotherapies are needed for patients with multiple myeloma (MM), since disease recurrence remains a major obstacle. B-cell maturation antigen (BCMA), a cell surface protein universally expressed on malignant plasma cells , has emerged as a very selective antigen to be targeted in novel treatments for MM. We here first review BCMA-related biology, and then highlight the recent clinical development of a novel afucosylated anti-BCMA monoclonal antibody conjugated with monomethyl auristatin F via noncleavable linker (GSK2857916). Chimeric antigen receptor-expressing T cells targeting BCMA may also induce specific and durable anti-MM responses by patients' own effector cells. Clinical trials testing these two approaches (NCT02064387, NCT02215967) are currently ongoing in relapsed and refractory MM patients., Competing Interests: Financial & competing interests disclosure Y-T Tai is a consultant for Onyx. KC Anderson serves on advisory boards to Onyx, Celgene, Gilead, Bristol-Myers Squibb and Sanofi-Aventis and is a scientific founder of Acetylon and Oncopep. Funding: NIH grants RO1050947, PO1-CA078378 and DF/HCC SPORE in Multiple Myeloma P50CA100707; KC Anderson is an American Cancer Society Clinical Research Professor. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.

Hematopoietic stem cell transplantation is the treatment of choice for many hematologic malignancies and genetic diseases. However, viral infections continue to account for substantial post-transplant morbidity and mortality. While antiviral drugs are available against some viruses, they are associated with significant side effects and are frequently ineffective. This review focuses on the immunotherapeutic strategies that have been used to prevent and treat infections over the past 20 years and outlines different refinements that have been introduced with the goal of moving this therapy beyond specialized academic centers.