New Genetically Engineered Immunotherapy
T cell-based immunotherapy represents one of the most promising emerging treatments for advanced cancers. While cancer cells employ strategies to evade the body's immune system, immunotherapy seeks to overcome those deceits so that T cells recognize and become cytotoxic to cancer cells. One of the ways to do this is with chimeric antigen receptor (CAR)-T cell therapy, a form of adoptive cell transfer in which a patient's T cells are extracted through apheresis, genetically engineered to develop receptors that bind to a specific antigen expressed on the surface of cancer cells, and infused back into the patient.
Adoptive cell transfer represents an area of basic and clinical research that the University of Maryland Marlene Stewart Greenebaum Comprehensive Cancer Center has been exploring for several years through its Tumor Immunology and Immunotherapy program. Through clinical trials, many UMGCCC patients, including a multiple myeloma survivor of more than 15 years, have benefited from gene-modified immune cells.
Now, CAR-T cell therapies are becoming mainstream treatment options. In August and October 2017, the FDA approved the first two gene therapies available in the United States, the latter of which is Yescarta (axicabtagene ciloleucel), a CAR-T cell therapy that targets B-cell lymphoma. Because of its large blood and marrow transplant service and depth of experience in administering adoptive cell transfer immunotherapy trials, UMGCCC was one of the first centers – and the only one in the Baltimore-Washington-Virginia area – chosen by Kite Pharma to offer Yescarta. The FDA requires centers to be certified to administer Yescarta so that their staffs are trained to handle the serious side effects that often accompany the therapy. Though CAR-T cell therapy comes with risks, 51 percent of the patients who received Yescarta on a multi-center trial showed no evidence of the cancer despite failing two or more therapies previously.
CAR-T cell therapy is just one of the many forms of immunotherapy available to cancer patients at the University of Maryland. UMGCCC's robust research program in Tumor Immunology and Immunotherapy was established in 2006, and today the program boasts nearly 50 clinical and basic research investigators. The press release below contains more details about this new therapy available at UMGCCC. To inquire about this therapy, call 410-328-7904.
- University of Maryland Greenebaum Comprehensive Cancer Center Now among Select Institutions Certified to Administer CAR T-cell Therapy for Lymphoma (Press Release)
- Current Immunotherapy Trials at UMGCCC
- Tumor Immunology and Immunotherapy Research Program
- Patients' Own Genetically Altered Immune Cells Show Promise in Fighting Blood Cancer (Press Release)
- Investigator-Initiated Trial Test Immunotherapy Drug for Acute Myeloid Leukemia (AML)
- Proposed GeneTrack tool to monitor adverse events related to CAR-T cell therapy
Strategies Cancers Use to Evade the Immune System
- Geng D, Kaczanowska S, Tsai A, Younger K, Ochoa A, Rapoport AP, Ostrand-Rosenberg S, Davila E. TLR5 ligand-secreting T cells reshape the tumor microenvironment and enhance antitumor activity. Cancer Res. 2015 May 15;75(10):1959-71.
- Rapoport, A. Myeloma escape from immunity: an "inside" job. Blood. 2015;126:1401-3.
- Jain A, Kaczanowska S, Davila E. IL-1 Receptor-Associated Kinase Signaling and Its Role in Inflammation, Cancer Progression, and Therapy Resistance. Front
Immunol. 2014 Nov 17;5:553. Review.
Engineered T Cells
- Kaczanowska S, Joseph AM, Guo J, Tsai AK, Lasola JJ, Younger K, Zhang Y, Gonzales CV, Davila E. A Synthetic CD8?:MyD88 Coreceptor Enhances CD8+ T-cell Responses to Weakly Immunogenic and Lowly Expressed Tumor Antigens. Cancer Res. 2017 Dec; 77(24):7049-58.
- Bollino D, Webb TJ. Chimeric antigen receptor-engineered natural killer T cells for cancer immunotherapy. Transl Res. 2017 Sep187:32-43.
- Tsai AK, Davila E. Producer T cells: Using genetically engineered T cells as vehicles to generate and deliver therapeutics to tumors. Oncoimmunology. 2016 Jan;5(5):e1122158.
- Katz SC, Point GR, Cunetta M, Thorn M, Guha P, Espat N, Boutros C, Hanna N, Junghans RP. Regional CAR-T cell infusions for peritoneal carcinomatosis are superior to systemic delivery. Cancer Gene Ther. 2016 May;23(5):142-8.
- Rapoport A, et al. NY-ESO-1-specific TCR-engineered T cells mediate sustained antigen-specific antitumor effects in myeloma. Nat Med. 2015 Aug;21(8):914-21.
- Rapoport AP, Aqui NA, Stadtmauer EA, Vogl DT, Xu YY, et al. Combination immunotherapy after ASCT for multiple myeloma using MAGE-A3/Poly-ICLC immunizations followed by adoptive transfer of vaccine-primed and costimulated autologous T cells. Clin Cancer Res. 2014 Mar 1;20(5):1355-65.
- Rapoport AP, Aqui N, Stadtmauer EA, Vogl DT, Fang HB, Cai L, Janofsky S, Chew A, Akpek G, Badros AZ, Yanovich S, Tan M, Veloso E, Pasetti M, Cross A, Philip S, Murphy H, Bhagat R, Zheng Z, Milliron T, Cotte J, Cannon A, Levine BL, Vonderheide RH, June CH. Combination immunotherapy using adoptive T-cell transfer and tumor antigen vaccination based on hTERT and surviving following ASCT for myeloma. Blood. 2011; 117(3): 788-97.
- Rapoport AP, Stadtmauer EA, Aqui N, Badros AZ, Cotte J, et al. Restoration of immunity in lymphopenic cancer patients by vaccination and adoptive T-cell transfer. Nat Med. 2005 Nov;11(11):1230–7.
Strategies to Overcome the Immunosuppressive Tumor Environment (TME)
- Joseph AM, Srivastava R, Zabaleta J, Davila E. Cross-talk between 4-1BB and TLR1-TLR2 Signaling in CD8+ T Cells Regulates TLR2's Costimulatory Effects. Cancer Immunol Res. 2016 Aug;4(8):708-16.
- Tiper IV, Temkin SM, Spiegel S, Goldblum SE, Giuntoli RL 2nd, Oelke M, Schneck JP, Webb TJ. VEGF Potentiates GD3-Mediated Immunosuppression by Human Ovarian Cancer Cells. Clin Cancer Res. 2016 Aug 15;22(16):4249-58.
- Kaczanowska S, Davila E. Ameliorating the tumor microenvironment for antitumor responses through TLR5 ligand-secreting T cells. Oncoimmunology. 2015 Aug 20;5(4):e1076609.