ACTIVE IMMUNOTHERAPY OF L1210 LEUKAEMIA APPLIED AFTER GRAFT OF TUMOUR CELLS

(1) In the first experiment, a comparison was made of the effects of BCG, Corynebacterium parvum, Mycobacterium cheiloni, Bordetella pertussis or irradiated leukaemic cells, administered once or several times after the graft of 104 L1210 leukaemic cells. Of the adjuvants, BCG was the only one with any notable effect, and repeated administration was more active than when given as a single dose; the irradiated leukaemic cells were more active than BCG, and had identical activity whether they were injected once or repeatedly. (2) In the second experiment, a comparison was made of the effects of BCG, of irradiated leukaemic cells and a combination of them both, administered at various times in relation to a graft of 104 L 1210 leukaemic cells. The BCG was given as repeated doses, whilst the irradiated leukaemic cells were given as a single dose. The BCG was more effective than the irradiated leukaemic colls when they were administered before the graft of the leukaemia; the irradiated leukaemic cells were more effective when they were given after the graft of the leukaemia. A combination of the two forms of immunotherapy was more effective than BCG alone, even when this was administered before the graft of the leukaemia, and more active than the irradiated leukaemic cells, even when they were administered after the graft of the leukaemia. (3) In the third experiment, (C57BL/6 × DBA/2)F1 mice were grafted with a variable number of L1210 (DBA/2) leukaemic cells. They were then treated during the 24 hours which followed this graft by active immunotherapy, either non-specific, using BCG, or specific, using leukaemic cells that had been irradiated at 15,000 rads, or by a combination of both. The three procedures were confirmed not only to be capable of prolonging the survival of the mice but also curing a considerable number of them. But cure was only obtained in those groups of animals in which the number of grafted cells was 105 or fewer. When larger numbers of leukaemic cells were grafted the treatment was ineffective. (4) The possible clinical application of these findings is discussed. They have already been applied to a trial of active immunotherapy for the treatment of acute lymphoblastic leukaemia in man, and have shown that such a therapy can be effective. This work was supported by a grant from I.N.S.E.R.M., No. 66-235. © 1969, The British Empire Cancer Campaign for Research. All rights reserved.