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Exosomes, a subset of extracellular vesicles, are released by all active cells and play a crucial role in intercellular communications. Exosomes could facilitate the transfer of various biologically active molecules, such as DNA, non-coding RNAs, and proteins, from donor to recipient cells, thereby participating in diverse biological and pathological processes. Besides, exosomes possess unique characteristics, including non-toxicity, low-immunogenicity, and stability within biological systems, rendering them highly advantageous for cancer drug development. Meanwhile, accumulating evidence suggests that exosomes originating from tumor cells and immune cells possess distinct composition profiles that play a direct role in anticancer immunotherapy. Of note, exosomes can transport their contents to specific cells, thereby exerting an impact on the phenotype and immune-regulatory functions of targeted cells. Therapeutic cancer vaccines, an emerging therapeutics of immunotherapy, could enhance antitumor immune responses by delivering a large number of tumor antigens, thereby augmenting the immune response against tumor cells. Therefore, the therapeutic rationale of cancer vaccines and exosome-based immunotherapy are almost similar to some extent, but some challenges have hindered their application in the clinical setting. Here, in this review, we first summarized the biogenesis, structure, compositions, and biological functions of exosomes. Then we described the roles of exosomes in cancer biology, particularly in tumor immunity. We also comprehensively reviewed current exosome-based anticancer vaccine development and we divided them into three types. Finally, we give some insights into clinical translation and clinical trial progress of exosome-based anticancer vaccines for future direction. • Exosomes are crucial mediators in normal biological processes and cancer development. • Exosomes have dual-effects in immune microenvironment of tumors. • Exosomes could be applied as therapeutic cancer vaccines to induce antitumor immune responses. • The translational application and clinical trials of exosome-based anti-cancer vaccines are promising but challenging. [ABSTRACT FROM AUTHOR]

• NK cells are safe in allogeneic applications and therefore are ideal off-the-shelf drugs. • NK cell-based therapeutics have shown satisfying safety profiles and promising efficiency in cancer treatment. • NK cells possess a reservoir of innate immune receptors targeting various types of cancer cells. • With proper engineering, NK cells can function as the universal anti-cancer drugs that are not restricted to HLA and cancer types. Natural killer (NK) cell therapy is emerging as a cancer treatment. NK cells are innate cytotoxic lymphocytes that act as first-line responders to kill target cells without prior encounters. NK cells recognize cancer cells, virus-infected cells, and other types of stressed cell through a reservoir of germline-encoded receptors. NK cells are safe for allogeneic applications. Therefore, they are the ideal off-the-shelf cell, which overcome the low efficiency issue caused by the patient-by-patient nature of autologous cell therapy. Unlike T cells, NK cells cannot form a strong immune memory; therefore, they suffer from short in vivo persistence. However, different from T cells, NK cells have a reservoir of innate immune receptors targeting a variety of malignant cells. In addition, they can utilize antibody guidance in target recognition. With suitable engineering, NK cells can function as universal anticancer drugs that are not restricted to HLA and cancer types, which will benefit the large cohort of patients with rare cancer types and patients with no convenient drug targets for precision and personalized medicine. Here, we summarize and discuss the designs of current anticancer NK cell therapies. [ABSTRACT FROM AUTHOR]

Drug conjugates are conjugates comprising a tumor-homing carrier tethered to a cytotoxic agent via a linker that are designed to deliver an ultra-toxic payload directly to the target cancer cells. This strategy has been successfully used to increase the therapeutic efficacy of cytotoxic agents and reduce their toxic side effects. Drug conjugates are being developed worldwide, with the potential to revolutionize current cancer treatment strategies. Antibody-drug conjugates (ADCs) have developed rapidly, and 14 of them have received market approval since the first approval event by the Food and Drug Administration in 2000. However, there are some limitations in the use of antibodies as carriers. Other classes of drug conjugates are emerging, such as targeted drugs conjugated with peptides (peptide-drug conjugates, PDCs) and polymers (polymer-drug conjugates, PolyDCs) with the remaining constructs similar to those of ADCs. These novel drug conjugates are gaining attention because they overcome the limitations of ADCs. This review summarizes the current state and advancements in knowledge regarding the design, constructs, and clinical efficacy of different drug conjugates. [ABSTRACT FROM AUTHOR]