Tumor-specific activated memory T cells have antitumor effects

Specifically activated memory T cells from cancer patients can recognize and reject autologous tumors transplanted into mice, according to a report in the July issue of the Journal of Clinical Investigation.

“The bone marrow of breast cancer patients (and perhaps in patients with other tumors) is enriched for tumor-specific memory T lymphocytes,” Dr. Viktor Umansky from German Cancer Research Center, Heidelberg, Germany told Reuters Health. “They can be isolated, in vitro re-activated with autologous bone marrow dendritic cells loaded with tumor-specific antigens, and selectively infiltrate tumor tissue after the transfer in vivo.”Dr. Umansky and colleagues isolated bone marrow-derived na?ve or memory T cells, stimulated them with autologous dendritic cells pulsed with tumor lysate, and transferred them into NOD/SCID mice bearing autologous breast tumors and normal skin transplants.Tumor antigen-specific memory T cells from patients’ bone marrow are apparently primed by tumor antigens from their own marrow and can recognize and react to such antigens presented on dendritic cells, the authors report. These activated memory T cells (but not activated na?ve T cells) can selectively home to xenotransplanted tumor in mice after adoptive transfer.Memory cells were able to infiltrate autologous human tumor transplants and peripheral nonlymphatic tumor tissue, the results indicate, but the cells did not infiltrate autologous normal skin transplants.Both central memory and effector memory T cells (but not na?ve T cells) expressed perforin, the researchers note, and tumor regression was directly related to the presence of large numbers of perforin-expressing T cells around tumor lobules, as well as the emergence of multiple apoptotic cells within the tumor lobules.”Our findings suggest that both memory subsets derived from bone marrow of cancer patients can be responsible for the observed therapeutic effects,” the investigators conclude. “Effector memory T cells can efficiently provide an immediate local response on the basis of their reduced activation requirements and increased frequency. In contrast, central memory T cells are capable of rapidly generating a large number of effector cells based on their high proliferative capacity and ability to differentiate into effectors.””Tumor-reactive memory T cells could be a good source for generating effector cells for immunotherapy of cancer patients in the absence of adverse autoimmune responses,” Dr. Umansky said.”Now we are investigating whether tumor-specific memory T cells pre-exist in the bone marrow of patients with other tumors (e.g., with melanoma or myeloma),” Dr. Umansky added. “In addition, we are beginning a phase I clinical trial, in which bone marrow memory T cells and dendritic cells are isolated from the breast cancer patient, in vitro re-stimulated, and transferred back into the same patient.”(Source: J Clin Invest 2004;114:67-76: Reuters Health: Will Boggs, MD: Oncolink: July 2004)