Adoptive immunotherapy effective in mice with metastatic prostate cancer

Adoptive immunotherapy using lymphocytes programmed to target bone lesions is effective in a mouse model, according to a report in the December issue of the Journal of Clinical Investigation.

This “T body” approach combines the effector functions of T lymphocytes and NK cells with the ability of antibodies to target predefined surface antigens and thereby to home to prostate cancer bone lesions.”The combination of gene delivery technology to redirect the specificity of T cells and the trafficking and homing ability as well as the effector function of such cells holds a great promise for cancer therapy,” Dr. Zelig Eshhar from The Weizmann Institute of Science, Rehovot, Israel told Reuters Health.Dr. Eshhar hypothesized that treatments that induce SDF-1 expression in the bone marrow would increase the homing and retention of T cells genetically engineered to target prostate cancer cells. They tested their hypothesis in severe combined immunodeficiency (SCID) mice.Pretreatment of the mice with irradiation significantly increased SDF-1 expression, the authors report, and engineered T lymphocytes (T bodies) repopulated the murine bone marrow to a greater extent after this conditioning.Specific antitumor effects were achieved only in mice that were treated after the preconditioning regimen, the researchers note.Four of 11 mice treated with T bodies after pretreatment with cyclophosphamide maintained low serum levels of prostate-specific antigen (PSA) for as long as 2 months after treatment, the results indicate.”Of the two pretreatments,” the investigators write, “cyclophosphamide was more effective in creating the proper conditions to enable the chimeric receptor-bearing lymphocytes to exert their therapeutic effect in SCID mice.””Taken together, our results suggest that tumor-specific T bodies are attracted by SDF-1 to migrate to the bone marrow, where they eradicate tumor cells,” the authors conclude.”Targeted cellular immunotherapy is a valid and safe option (and in some cases the only one) for incurable advanced cancer,” Dr. Eshhar explained. “Preconditioning of patients, using relatively mild treatments, can be used to significantly improve the clinical outcome of adoptive cellular therapy.””There is sufficient evidence from animal studies that the T-body approach can serve as targeted immunotherapy of colon, kidney, and lymphoma cancers,” Dr. Eshhar said. “We plan to optimize the approach, attempting to further improve the trafficking of redirected T-cells to disseminated cancer and increase the functionality and persistence of the adoptively transferred cells in the recipients.”(Source: J Clin Invest 2004;114:1774-1781: Reuters Health: Oncolink: December 2004.)