An Experimental Screening for “Systemic Adjuvants of Immunity” Applicable in Cancer Immunotherapy¹

Ten agents, Bacillus Calmette-Guérin, methanol extract residual and two other extracts of mycobacteria, Corynebacterium parvum, three preparations of Corynebacterium granulosum, Polyinosinic-polycytidylic acid, and polyadenylic-polyuridylic acid have been shown by one or several previous experiments to be able to stimulate immune responses. These agents were submitted to a screening battery, the object of which was to detect “systemic adjuvants of immunity” useful in cancer immunotherapy. The tests of this battery are: (a) the hemolytic plaque-forming cell test, (Jerne), which produces an immune reaction requiring thymus-derived and bone marrow-derived lymphocyte cooperation, enabling us to study the factors of time and route of administration; (b) the graft-versus-host reaction which produces an immune reaction involving only thymus-derived lymphocytes, enabling us to study the route of administration factor; and (c) the immunoprophylaxis of three murine tumors, a leukemia (L1210), and two solid tumors (Lewis' tumor and ICIG CI₁), which permitted us to study the route of administration factor.

This work showed that agents considered as immunity adjuvants are immunostimulators under some conditions but may be immunodepressors under other conditions, not only in the Jerne test but also in the graft-versus-host reaction. It also showed that, while their effect is nil or favorable as far as immunoprophylaxis of L1210 leukemia is concerned, it may be nil, favorable, or unfavorable (growth enhancement) in the Lewis solid tumor and in the ICIG CI₁ solid tumor.

Therefore, this screening battery can be used to detect new systemic adjuvants of immunity applicable in cancer immunotherapy or immunoprophylaxis and gives preliminary but necessary information concerning their pharmacokinetics. The results obtained on solid tumor prophylaxis make us cautious about their use in clinical immunotherapy trials on solid tumors, but they give no indication against their use in leukemia.