Adoptive cell transfer

Adoptive cell transfer (ACT) is the transfer of cells into a patient. The cells may have originated from the patient or from another individual. The cells are most commonly derived from the immune system with the goal of improving immune functionality and characteristics. In autologous cancer immunotherapy, T cells are extracted from the patient, genetically modified and cultured in vitro and returned to the same patient. Comparatively, allogeneic therapies involve cells isolated and expanded from a donor separate from the patient receiving the cells.

In the 1960s, lymphocytes were discovered to be the mediators of allograft rejection in animals. Attempts to use T cells to treat transplanted murine tumors required cultivating and manipulating T cells in culture. Syngeneic lymphocytes were transferred from rodents heavily immunized against the tumor to inhibit growth of small established tumors, becoming the first example of ACT.

Description of T cell growth factor interleukin-2 (IL-2) in 1976 allowed T lymphocytes to be grown in vitro, often without loss of effector functions. High doses of IL-2 could inhibit tumor growth in mice. 1982, studies demonstrated that intravenous immune lymphocytes could treat bulky subcutaneous FBL3 lymphomas. Administration of IL-2 after cell transfer enhanced therapeutic potential.

In 1985 IL-2 administration produced durable tumor regressions in some patients with metastatic melanoma. Lymphocytes infiltrating the stroma of growing, transplantable tumors provided a concentrated source of tumor-infiltrating lymphocytes (TIL) and could stimulate regression of established lung and liver tumors. In 1986, human TILs from resected melanomas were found to contain cells that could recognize autologous tumors. In 1988 autologous TILs were shown to reduce metastatic melanoma tumors. Tumor-derived TILs are generally mixtures of CD8⁺ and CD4⁺ T cells with few major contaminating cells.

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