IMMUNITY IN TUMOR TRANSPLANTATION 409 



is grafted into a rat, the tumor, as a rule, after a temporary growth retro- 

 gresses, and then a second inoculation of a similar tumor into the same host 

 does not lead even to the limited growth shown by the first transplant. The 

 animal has become immune as the result of the growth and retrogression of 

 the first tumor. In accordance with what we know as to the inability of autog- 

 enous tumors to elicit immunity of this kind, is the great infrequency with 

 which spontaneous tumors retrogress; but if they do retrogress, this is pre- 

 sumably brought about by factors other than immunity, or by an immunity 

 not directed against the organismal differentials but against other substances. 



As stated above, we must conceive of the immunity following retrogression 

 of a tumor as a variety of concomitant immunity, which primarily is due to 

 the dissimilarity and incompatibility of the organismal differentials of tumor 

 and host. As the result of this incompatibility the primary, preformed homoio- 

 or heterotoxins of the host injure the transplant and the strange individu- 

 ality or species differentials of the grafted tumor may act as antigen, eliciting 

 the production of immune bodies, which then support and complete the effect 

 of the primary homoio- or heterotoxins ; and it is probable that these immune 

 substances are mainly responsible for the injury of the transplant and the 

 subsequent cessation of its growth and its retrogression. In addition, during 

 retrogression of the tumor, tumor material is being absorbed, which also may 

 serve as antigen and cause additional formation of antibodies. 



The retrogression immunity is very effective and may cause the shrinking 

 and the ultimate disappearance of tumors which had already been established 

 in the host, and which had successfully passed through the early, dangerous 

 stages following transplantation. As a result of this immunity the tumor it- 

 self, which has given rise to the production of the immunity, experiences the 

 effect of its own activity and undergoes complete retrogression. A subsequent 

 second inoculation of a tumor piece is then unsuccessful. After the tumor 

 has once been absorbed, the animal organism is no longer able to neutralize 

 the immune substances which may still continue to be produced. We believe, 

 therefore, that also this type of immunity, against the growth of a transplanted 

 tumor, is not merely caused by the retrogression of a tumor, but that it already 

 sets in some time preceding the retrogression and continues during this 

 process, and that it is intensified through the absorption of material from the 

 retrogressing tumor. There follows then a struggle between the host, which 

 produces substances injurious to the tumor, and the inherent growth energy 

 of the tumor combined with its power to neutralize injurious substances; in 

 addition, there may perhaps come into play also certain adaptive processes in 

 the cancer cells. 



The increase in immunity which takes place during the retrogression of 

 the tumor must in some way depend on the activity of the living, metabolically 

 still potent tumor cells. This is indicated by the fact that when we produced 

 retrogression of a first mouse carcinoma IX by exposing the tumor, previous 

 to transplantation, to a degree of heat sufficient to injure the tumor cells 

 markedly and thus experimentally to induce the subsequent retrogression 

 of the grafted tumor, the immunity resulting from this retrogression was 



