Immunotoxin Therapy of Solid and Hematopoietic Tumors: Preclinical Studies

Division Of Basic Sciences - Nci

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Abstract

Because we observed that some patients treated with immunotoxins developed anti-tumor immunity, we have developed a syngeneic mouse tumor model to study interactions of the immune system with immunotoxin therapy. We have developed syngeneic mouse models to evaluate the combination of LMB-100 and check point inhibitors. We find that the direct injection of LMB-100 into tumors synergizes with anti-CTLA-4 given I.P. to produce complete tumor regressions and the development of anti-tumor immunity. These studies were done in a mouse breast cancer model and have been extended to other cancer types (mesothelioma, colon cancer). We evaluated various check point inhibitors and found that only anti-CTLA-4 IgG2a was active in our model. We are now conducting clinical trials with these agents. To develop a new treatment for myeloma we have made new immunotoxins targeting BCMA that is expressed on almost all myelomas. We find the anti-BCMA immunotoxins are very active in 2 models of myeloma and are investigating how best to combine immunotoxins with other anti-myeloma therapies. We have developed a new antibody to mesothelin (Mab15B6) that binds very close to the plasma membrane and are using it to make CAR-T cells and bispecific antibodies. Preliminary evidence shows that CAR-T cells are very effective in killing mesothelin expressing cancer cells.