Engineering immune-evasive allogeneic cellular immunotherapies Review
| Authors: | Martin, K. E.; Hammer, Q.; Perica, K.; Sadelain, M.; Malmberg, K. J. |
| Review Title: | Engineering immune-evasive allogeneic cellular immunotherapies |
| Abstract: | Allogeneic cellular immunotherapies hold a great promise for cancer treatment owing to their potential cost-effectiveness, scalability and on-demand availability. However, immune rejection of adoptively transferred allogeneic T and natural killer (NK) cells is a substantial obstacle to achieving clinical responses that are comparable to responses obtained with current autologous chimeric antigen receptor T cell therapies. In this Perspective, we discuss strategies to confer cell-intrinsic, immune-evasive properties to allogeneic T cells and NK cells in order to prevent or delay their immune rejection, thereby widening the therapeutic window. We discuss how common viral and cancer immune escape mechanisms can serve as a blueprint for improving the persistence of off-the-shelf allogeneic cell therapies. The prospects of harnessing genome editing and synthetic biology to design cell-based precision immunotherapies extend beyond programming target specificities and require careful consideration of innate and adaptive responses in the recipient that may curtail the biodistribution, in vivo expansion and persistence of cellular therapeutics. © Springer Nature Limited 2024. |
| Keywords: | transplantation, homologous; gene deletion; genetics; nonhuman; neoplasm; neoplasms; cd8+ t lymphocyte; t lymphocyte; t-lymphocytes; mouse; animal; animals; immune system; multiple myeloma; prevalence; rna interference; cyclophosphamide; melphalan; hematopoietic stem cell transplantation; cytotoxicity; histology; cost effectiveness analysis; t lymphocyte receptor; immunological tolerance; immunology; cellular immunity; immune response; fibrosarcoma; immunotherapy; gamma interferon; genetic engineering; immunogenicity; hla dr antigen; cd4+ t lymphocyte; rat; tumor cell; chimeric antigen receptor; natural killer cell; killer cells, natural; immunomodulation; upregulation; gene dosage; phagocytosis; immunosuppressive treatment; major histocompatibility complex; tacrolimus; plerixafor; therapy; adoptive immunotherapy; antigen presenting cell; immunotherapy, adoptive; t lymphocyte activation; cd19 antigen; allotransplantation; cell killing; cd33 antigen; thymocyte antibody; antibody dependent cellular cytotoxicity; complement dependent cytotoxicity; personalized medicine; immunization; tumor microenvironment; neutralizing antibody; tumor escape; synthetic biology; procedures; xenotransplantation; therapeutic index; complement activation; cellular immunotherapy; humans; human; article; complement deposition; gene editing; crispr-cas9 system; mass cytometry; chimeric antigen receptor t-cell immunotherapy; receptors, chimeric antigen; antigenic escape; allogenic cell; positive and negative syndrome scale |
| Journal Title: | Nature Reviews Immunology |
| Volume: | 24 |
| Issue: | 9 |
| ISSN: | 1474-1733 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2024-09-01 |
| Start Page: | 680 |
| End Page: | 693 |
| Language: | English |
| DOI: | 10.1038/s41577-024-01022-8 |
| PUBMED: | 38658708 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PDF -- Source: Scopus |
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