Theme 5: Antibody and T-cell therapeutics

Overview:  Several CCIR members are developing antibody and T cell therapies for different types of cancer and finding ways to improve their efficacy.  Much progress has been made recently in the clinical use of antibodies and T cells for cancer therapeutics. Antibodies that target immune checkpoints have been effective in patients with metastatic cancer, and one of these, anti-CTLA-4, pioneered by Dr. James Allison, a new member of the CCIR, has been FDA approved for the treatment of metastatic melanoma. Dr. Allison’s work has opened a new field of utilizing antibodies against immune checkpoints, and other similar antibodies, such as anti-PD1 antibody, have been found to be effective against melanoma as well as renal cancer and lung cancer in patients with metastatic disease. In addition, antibodies that block regulatory immune cell function or activate co-stimulatory molecules, such as anti-OX40, have significant promise. Another modality that has shown significant promise in the clinic is the adoptive transfer of activated T cells. This therapy has been effective in patients with metastatic melanoma, and with genetic engineering using chimeric antigen receptor genes (CAR), T cells can be armed to attack other common cancers, such as leukemias and lymphoma.  Clinical development of reagents or strategies as a form of immunotherapy and advancement of cancer immunotherapies are ongoing.

Some highlights from the past year include:  
• A phase 2 clinical study, completed at the MD Anderson Cancer Center, showed that the combination of pidilizumab plus rituximab is well tolerated and active in patients with relapsed follicular lymphoma, suggesting that immune checkpoint blockade is worthy of further study in follicular lymphoma (Westin JR, Lancet Oncol. 2014)
• Treatment of patient-derived chemotherapy-resistant acute myelogenous leukemia with a novel T cell receptor-like mAb to PR1/HLA-A2, developed by CCIR investigators, eliminated leukemia stem cells in a xenograft model (Sergeeva A, In Press, 2014)
• A preclinical study found that adoptive T-cell transfer (ACT) with melanoma-specific T cells was much more effective in the context of concurrent BRAF inhibition, which led to increased T-cell infiltration of tumors that could be attributed largely to decreased VEGF production by the tumor cells (Liu CW, Clin Cancer Res. 2012)

Additional Relevant Publications: