Clinical effects of infusions into chimpanzees of primed autologous cultured T-cells

Abstract

As a model to study the possible early side effects of cultured T-cells (CTC) as a potential for adoptive cellular immunotherapy of human tumors, chimpanzees received iv infusions of 10(9) autologous, mixed lymphocyte culture-primed CTC. Complete blood counts, urinalyses, chest X-rays, blood chemistries, and serum immunoelectrophoresis were normal, and serologic studies were negative throughout the 3 weeks of observation. Serial transaminase levels were followed in 2 chimps, and mild increases in serum glutamic-oxaloacetic transaminase were seen in both and serum glutamic-pyruvic transaminase in 1 at 24 hours following each CTC infusion, but the levels returned to normal within 7 days. A liver biopsy specimen was normal. Fluorescence-activated cell sorter analysis of cells incubated with day 28 serum revealed weak labeling of only phytohemagglutinin (PHA)-stimulated lymphoblasts and of CTC, suggesting that a weak anti-PHA antibody was generated. These studies indicate that infusions of autologous, in vitro-primed CTC are accompanied by little clinical toxicity in the chimp model but that they may be weakly immunogenic.