Adoptive chemoimmunotherapy has cured experimentally induced tumors in animals, but its clinical use has been limited. Six patients were treated with refractory neoplasms in a Phase I study with cyclophosphamide (CPM) and alloactivated haploidentical lymphocytes. Patients received an immunosuppressive dose of CPM (800 mg/m2) followed by haploidentical lymphocytes primed in vitro with alloantigens in mixed lymphocyte culture (MLC). One week later patients received a second infusion of alloactivated lymphocytes expanded in T‐cell growth factor (TCGF). The total number of cells given to each patient progressively increased, with a single patient receiving 35.5 X 109 cells. Transient febrile responses and delayed‐type hypersensitivity reactions at the intravenous sites were the only toxicities noted. A complete clinical response lasting 12 weeks was seen in a single patient with diffuse histiocytic lymphoma. Our experience indicates that adoptive chemoimmunotherapy can be given to patients safely and merits further clinical testing.
A total of 13 cancer patients were treated with Adoptive Chemoimmunotherapy (ACIT) using alloactivated HLA haploidentical lymphocytes. Donor lymphocytes were activated in vitro using a pool of irradiated allogeneic lymphocytes (MLC-cells) and some further expanded by culturing in T-cell growth factor (TCGF-cells). The first 6 patients received i.v. cyclophosphamide (CPM) followed 24 h later by escalating doses of MLC-cells, then 7 days later they received an infusion of TCGF-cells. Minimal toxicity was seen. The next 7 patients received CPM (800 mg/m2) and a combined MLC and TCGF-cell infusion (total cell dose ranged from 0.79 x 10(10) to 2.26 x 10(10)). Of these 7 patients, 3 developed mild graft-versus-host reaction (GVHR) which resolved without treatment, and 2 patients had progressive GVHR which was arrested by methylprednisolone (2 mg/kg). Peripheral blood lymphocytes from these 2 patients, during the GVHR, had increased activated T-cells (OKT-10+ and OK-Ia+). In vitro expansion, in TCGF, of these activated T-cells enabled HLA typing to prove they were of donor origin. Only 1 clinical antitumor response was observed in the first 6 patients. The results of this study indicate that this form of ACIT can be given to patients with acceptable toxicity. Self-limited or easily controlled GVHR may be induced and primed donor cells persisting in the circulation are probably responsible. Further testing is required to determine whether the immune response induced by this form of ACIT may be therapeutically effective.
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