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Simple Summary: Cancer is basically a tough condition on a patient's body where cell grows uncontrollably. Normal cells are affected, which destroys the health of the patient. The main problem in cancer is spreading from one part to another. Therefore, the mathematical modeling of cancerous tumors integrates to check overall stability. A novel approach is introduced such as Bernstein polynomial with combination of genetic algorithm, sliding mode controller, and synergetic control. The proposed solution has easily eliminated cancerous cells within five days using synergetic control. In addition, five cases are incorporated to evaluate error function. In addition, a brief comparative study is added to contrast the simulation results with theoretical modeling. Cancerous tumor cells divide uncontrollably, which results in either tumor or harm to the immune system of the body. Due to the destructive effects of chemotherapy, optimal medications are needed. Therefore, possible treatment methods should be controlled to maintain the constant/continuous dose for affecting the spreading of cancerous tumor cells. Rapid growth of cells is classified into primary and secondary types. In giving a proper response, the immune system plays an important role. This is considered a natural process while fighting against tumors. In recent days, achieving a better method to treat tumors is the prime focus of researchers. Mathematical modeling of tumors uses combined immune, vaccine, and chemotherapies to check performance stability. In this research paper, mathematical modeling is utilized with reference to cancerous tumor growth, the immune system, and normal cells, which are directly affected by the process of chemotherapy. This paper presents novel techniques, which include Bernstein polynomial (BSP) with genetic algorithm (GA), sliding mode controller (SMC), and synergetic control (SC), for giving a possible solution to the cancerous tumor cells (CCs) model. Through GA, random population is generated to evaluate fitness. SMC is used for the continuous exponential dose of chemotherapy to reduce CCs in about forty-five days. In addition, error function consists of five cases that include normal cells (NCs), immune cells (ICs), CCs, and chemotherapy. Furthermore, the drug control process is explained in all the cases. In simulation results, utilizing SC has completely eliminated CCs in nearly five days. The proposed approach reduces CCs as early as possible. [ABSTRACT FROM AUTHOR]

Simple Summary: (CAR)-T cell-based therapies have achieved substantial success against different haematological malignancies. However, results for solid tumours have been limited up to now, in part due to the fact that the immunosuppressive tumour microenvironment inactivates CAR-T cell clones. In this paper we study mathematically the competition of CAR-T and tumour cells, taking into account their immunosuppressive capacity. Using computer simulations, we show that the use of large numbers of CAR-T cells targetting the solid tumour antigens could overcome the immunosuppressive potential of cancer. To achieve such high levels of CAR-T cells we propose, and study in silico, the manufacture and injection of CAR-T cells targetting two antigens: CD19 and a tumour-associated antigen. This strategy lead in our simulations to the expansion of the CAR-T cells injected and the production of a massive army of CAR-T cells targetting the solid tumour, and potentially overcoming its immune suppression capabilities. Thus, our proposed strategy could provide a way to develop successful CAR-T cell therapies against solid tumours. Chimeric antigen receptor (CAR)-T cell-based therapies have achieved substantial success against B-cell malignancies, which has led to a growing scientific and clinical interest in extending their use to solid cancers. However, results for solid tumours have been limited up to now, in part due to the immunosuppressive tumour microenvironment, which is able to inactivate CAR-T cell clones. In this paper we put forward a mathematical model describing the competition of CAR-T and tumour cells, taking into account their immunosuppressive capacity. Using the mathematical model, we show that the use of large numbers of CAR-T cells targetting the solid tumour antigens could overcome the immunosuppressive potential of cancer. To achieve such high levels of CAR-T cells we propose, and study computationally, the manufacture and injection of CAR-T cells targetting two antigens: CD19 and a tumour-associated antigen. We study in silico the resulting dynamics of the disease after the injection of this product and find that the expansion of the CAR-T cell population in the blood and lymphopoietic organs could lead to the massive production of an army of CAR-T cells targetting the solid tumour, and potentially overcoming its immune suppression capabilities. This strategy could benefit from the combination with PD-1 inhibitors and low tumour loads. Our computational results provide theoretical support for the treatment of different types of solid tumours using T cells engineered with combination treatments of dual CARs with on- and off-tumour activity and anti-PD-1 drugs after completion of classical cytoreductive treatments. [ABSTRACT FROM AUTHOR]

Simple Summary: Immune checkpoint inhibitors (ICIs) constitute a paradigm shift in cancer therapy, and it has greatly expanded our knowledge of anticancer immunity and has introduced breakthroughs in cancer therapy. However, despite the promising results in the use of immunotherapy in some cancers, numerous patients do not respond to ICIs without the existence of a clear predictive biomarker. This review provides an overview of recent advances in cellular and molecular factors within the tumor microenvironment (TME) to identify possible mechanisms of immunotherapy resistance, as well as to develop novel combination strategies for cancer immunotherapy. The in-depth exploration of complexity within the TME allows for the improvement of therapeutic efficacy and highlights its contribution to cancer immunotherapy. Immune checkpoints play critical roles in the regulation of T-cell effector function, and the effectiveness of their inhibitors in cancer therapy has been established. Immune checkpoint inhibitors (ICIs) constitute a paradigm shift in cancer therapy in general and cancer immunotherapy in particular. Immunotherapy has been indicated to reinvigorate antitumor T-cell activity and dynamically modulate anticancer immune responses. However, despite the promising results in the use of immunotherapy in some cancers, numerous patients do not respond to ICIs without the existence of a clear predictive biomarker. Overall, immunotherapy involves a certain degree of uncertainty and complexity. Research on the exploration of cellular and molecular factors within the tumor microenvironment (TME) aims to identify possible mechanisms of immunotherapy resistance, as well as to develop novel combination strategies involving the specific targeting of the TME for cancer immunotherapy. The combination of this approach with other types of treatment, including immune checkpoint blockade therapy involving multiple agents, most of the responses and effects in cancer therapy could be significantly enhanced, but the appropriate combinations have yet to be established. Moreover, the in-depth exploration of complexity within the TME allows for the exploration of pathways of immune dysfunction. It may also aid in the identification of new therapeutic targets. This paper reviews recent advances in the improvement of therapeutic efficacy on the immune context of the TME and highlights its contribution to cancer immunotherapy. [ABSTRACT FROM AUTHOR]

Simple Summary: Multimodal imaging systems with high registration accuracy and molecular agents with highly specific targeting capacity are vital for imaging-guided theranostics of cancer. A novel simultaneous dual-modal imaging system combined with cancer cell membrane-coated nanoparticles as an imaging-guided photothermal therapy (PTT) was reported in this paper. A novel detector with the ability to detect both high-energy X-ray and low-energy visible light at the same time, as well as a dual-modal imaging system based on the detector, was developed for intrinsic simultaneous dual-modal imaging. Cancer cell membrane-coated upconversion nanoparticles (CC-UCNPs) and gold nanoparticles (CC-AuNPs) with the capacity for immune evasion and active tumor targeting were engineered for highly specific imaging and high-efficiency PTT therapy. The highly specific imaging-guided PTT efficacy was evaluated both in vitro and in vivo. All these results suggested our biomimetic UCNP/AuNP and novel simultaneous dual-modal imaging combination could be a promising platform and methodology for cancer theranostics. Multimodal imaging-guided near-infrared (NIR) photothermal therapy (PTT) is an interesting and promising cancer theranostic method. However, most of the multimodal imaging systems provide structural and functional information used for imaging guidance separately by directly combining independent imaging systems with different detectors, and many problems arise when trying to fuse different modal images that are serially taken by inviting extra markers or image fusion algorithms. Further, most imaging and therapeutic agents passively target tumors through the enhanced permeability and retention (EPR) effect, which leads to low utilization efficiency. To address these problems and systematically improve the performance of the imaging-guided PTT methodology, we report a novel simultaneous dual-modal imaging system combined with cancer cell membrane-coated nanoparticles as a platform for PTT-based cancer theranostics. A novel detector with the ability to detect both high-energy X-ray and low-energy visible light at the same time, as well as a dual-modal imaging system based on the detector, was developed for simultaneous dual-modal imaging. Cancer cell membrane-coated upconversion nanoparticles (CC-UCNPs) and gold nanoparticles (CC-AuNPs) with the capacity for immune evasion and active tumor targeting were engineered for highly specific imaging and high-efficiency PTT therapy. In vitro and in vivo evaluation of macrophage escape and active homologous tumor targeting were performed. Cancer cell membrane-coated nanoparticles (CC-NPs) displayed excellent immune evasion ability, longer blood circulation time, and higher tumor targeting specificity compared to normal PEGylated nanoparticles, which led to highly specific upconversion luminescence (UCL) imaging and PTT-based anti-tumor efficacy. The anti-cancer efficacy of the dual-modal imaging-guided PTT was also evaluated both in vitro and in vivo. Dual-modal imaging yielded precise anatomical and functional information for the PTT process, and complete tumor ablation was achieved with CC-AuNPs. Our biomimetic UCNP/AuNP and novel simultaneous dual-modal imaging combination could be a promising platform and methodology for cancer theranostics. [ABSTRACT FROM AUTHOR]

Simple Summary: Combination of radiotherapy and immunotherapy to antagonize tumors is one of hotspot issues currently. Immunotherapy can effectively alleviate the non-lasting effect of radiotherapy and tumor recurrence. Local radiotherapy can mobilize immune cells into tumor microenvironment and make tumors unable to escape from immune supervision. Therefore, the radio-immunotherapy achieves better curative effects on cancer patients. We have reviewed the regulation of multiple immune cells with different functions by radiotherapy, as well as the mechanism research and clinical outcomes combined with immune checkpoint inhibitors for cancer treatment, which provides new insights in the treatment strategies for certain types of cancer patients in clinic. Radiotherapy (RT) is a conventional method for clinical treatment of local tumors, which can induce tumor-specific immune response and cause the shrinkage of primary tumor and distal metastases via mediating tumor infiltration of CD8+ T cells. Ionizing radiation (IR) induced tumor regression outside the radiation field is termed as abscopal effect. However, due to the mobilization of immunosuppressive signals by IR, the activated CD8+T cells are not sufficient to maintain a long-term positive feedback to make the tumors regress completely. Eventually, the "hot" tumors gradually turn to "cold". With the advent of emerging immunotherapy, the combination of immune checkpoint blockade (ICB) and local RT has produced welcome changes in stubborn metastases, especially anti-PD-1/PD-L1 and anti-CTLA-4 which have been approved in clinical cancer treatment. However, the detailed mechanism of the abscopal effect induced by combined therapy is still unclear. Therefore, how to formulate a therapeutic schedule to maximize the efficacy should be took into consideration according to specific circumstance. This paper reviewed the recent research progresses in immunomodulatory effects of local radiotherapy on the tumor microenvironment, as well as the unique advantage for abscopal effect when combined with ICB, with a view to exploring the potential application value of radioimmunotherapy in clinic. [ABSTRACT FROM AUTHOR]