Cancer Immunology & Immunotherapy

Program Leaders


 

Education and Training Liaison: Nina Shah, MD

Community Engagement Liaison: Bita Fakhri, MD, MPH

The overarching goals of the Cancer Immunology and Immunotherapy Program are to understand the molecular basis and dynamic relationship between the immune system and both hematopoietic and solid tumors to discover new strategies for cancer therapy.

 

  • Theme 1: Molecular mechanisms of hematological malignancies and immune responses to cancer
  • Theme 2: Cell-based therapies
  • Theme 3: Interplay between hematopoietic and solid tumors and the immune system

Scientific Accomplishments By Theme

Theme 1: Molecular mechanisms of hematological malignancies and immune responses to cancer

In collaboration with the Preclinical Therapeutics Core Facility, Thomas Martin, Jeffrey Wolf, and Nina Shah, Arun Wiita published evidence that the spliceosome is a therapeutic vulnerability in multiple myeloma. Adil Daud, in collaboration with Alain Algazi, Katy Tsai, Michael Rosenblum, and Lawrence Fong, published a series of reports on both the clinical efficacy and immune responses induced with IL-12 plasmid electroporation either alone or in combination with PD-1 blockade in melanoma patients. Adil Daud and Michael Rosenblum collaborated with Mallika Dhawan (MO), Pamela Munster (MO), Hope Rugo (BR), Mark Moasser (BR), and Michelle Melisko (BR), to report on an exhausted T cell signature associated with response to PD-1 blockade in ER-positive breast cancer. Continuing with their original identification of a neoantigen shared in patients with diffuse midline glioma, Hideo Okada has furthered evaluated the immunogenicity of this antigen using mass cytometry. In collaboration with Terence Friedlander (MO), David Oh, Matthew Spitzer and Lawrence Fong published single cell analysis of human bladder cancer identifying cytotoxic CD4 T cells that can mediate tumor killing.

Theme 2: Cell-based therapies

Charalambos Andreadis and collaborators published the results of a multicenter study of lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas that demonstrated a high objective response rate. In collaboration with colleagues from the US Lymphoma CAR T Consortium, Charalambos Andreadis confirmed high rates of response of axicabtagene ciloleucel in patients with relapsed or refractory large B-cell lymphoma. In conjunction with Lawrence Kaplan and Weiyun Ai, he also reported a case series of immune-related toxicities associated immune checkpoint inhibition in conjunction with CAR T-cell treatment. Lawrence Fong collaborated with Lloyd Damon and Andrew Ko (MO) to evaluate CARTs targeting mesothelin and CD19 in patients with pancreas cancer. Developing next generation CART, Kole Roybal, Alex Marson, and Jeffrey Bluestone have used CRISPR-based knock-in strategies to identify novel pathways that can be exploited in engineering these cells. Wendell Lim described a combinatorial approach to using multiple surface antigens to more selectively target solid tumors.

Theme 3: Interplay between hematopoietic and solid tumors and the immune system 

Thomas Martin published the results of a dose-finding study of the anti-CD38 mAb isatuximab in multiple myeloma patients. He collaborated with Jeffrey Wolf, Bin Liu and the Center’s Preclinical Therapeutics Core Facility to demonstrate substantial preclinical activity of an anti-ICAM1 antibody-drug conjugate in models of multiple myeloma. Members Thomas Martin, Jeffrey Wolf, Kole Roybal, Nina Shah, Jack Taunton (MO), and Arun Wiita collaborated with Martin Kampmann (MO) in a study of CRISPR-based screens to identify genes that influence responsiveness to immunotherapy in multiple myeloma. In collaboration with Thomas Martin, Jeffrey Wolf, Sandy Wong, Nina Shah and Huimin Geng (MO), Wiita’s lab demonstrated that DNMTIs can upregulate CD38 expression on the surface of myeloma cells, resulting in sensitization to daratumumab. Multiple lines of investigation have implicated the importance of different immune cell types in the tumor microenvironment in affecting anti-tumor responses including regulator T cells by Jeffrey Bluestone and Adil Daud, NK cells by Lewis Lanier and Lawrence Fong, and neutrophils by Clifford Lowell. Novel modes of immunosuppression were also identified by the group including integrin-mediated activation of TGF-B by James Marks, tension by Valerie Weaver, and autophagy-mediated degradation of MHC-1 by Rushika Perera. Finally, Matthew Spitzer used a systems biology approach to identified systemic immune dysfunction mediated by tumor growth.