Immunotherapeutic strategies leveraging the immune system’s antitumor activity have become a mainstay of cancer treatment. Strategies including antibody-directed approaches, stem cell transplantation, immunomodulatory drugs, immune checkpoint inhibitors, CAR T cells, and vaccines have demonstrated particular success in controlling and even eradicating hematological cancers. This Review Series, developed by JCI’s associate editor Leo Luznik, discusses ongoing progress in immunotherapeutic targeting of hematological cancers. Reviews will address the state-of-the-art in immunotherapies for acute myeloid leukemia, multiple myeloma, and lymphoma and highlight recent successes and challenges in clinical trials for these diseases; take a detailed look at recent developments in CAR T therapies for B cell malignancies; and describe how personalized antigen targeting can be applied to immunotherapeutic treatment of blood malignancies.
Lymphoid malignancies typically promote an infiltrate of immune cells at sites involved by the disease. While some of the immune cells present in lymphoma have effector function, the immune system is unable to eradicate the malignant clone. Therapies that optimize immune function therefore have the potential to improve the outcome of lymphoma patients. In this Review, we discuss immunologic approaches that directly target the malignant cell as well as approaches to optimize both the innate and adaptive immune response to the tumor. While many of these therapies have shown single-agent activity, the future will clearly require thoughtful combinations of these approaches.
Stephen M. Ansell, Yi Lin
Hematological malignancies have long been at the forefront of the development of novel immune-based treatment strategies. The earliest successful efforts originated from the extensive body of work in the field of allogeneic hematopoietic stem cell transplantation. These efforts laid the foundation for the recent exciting era of cancer immunotherapy, which includes immune checkpoint blockade, personal neoantigen vaccines, and adoptive T cell transfer. At the heart of the specificity of these novel strategies is the recognition of target antigens presented by malignant cells to T cells. Here, we review the advances in systematic identification of minor histocompatibility antigens and neoantigens arising from personal somatic alterations or recurrent driver mutations. These exciting efforts pave the path for the implementation of personalized combinatorial cancer therapy.
Livius Penter, Catherine J. Wu