Antibody responses of unconditioned Syrian hamsters to 4 heterotransplantable human tumors implanted at either cheek pouch, s.c., or i.p. sites were measured by a hemagglutination technic. The least effective site for immunization was the cheek pouch, whereas the i.p. site was the most effective. The antibody response was most rapid and intense to HeLa and H. Ep. No. 2 tumors, somewhat less rapid to KB, and significantly slower and less intense to H. Ad. No. 1 U tumor (Toolan's human adenocarcinoma No. 1 adapted to unconditioned hamsters). The latter tumor, the only 1 of the 4 employed which was serially transplantable in unconditioned hosts, was employed in studies of second-set reactions. Hamsters sensitized by a 12-day-old s.c. tumor implant rejected a second tumor implanted s.c. or in the cheek pouch, whereas growth of tumor in the cheek pouch for 12 days failed to induce a second-set rejection reaction. Thus the pouch prevented primary sensitization to H. Ad. No. 1 U but did not prevent second-set reactions in adequately sensitized hosts.

The cheek pouch barrier hypothesis and the limitations which the results of these studies impose thereon are discussed. It is concluded that the cheek pouch is not impervious to soluble antigens but may either impede dissemination of relatively insoluble cellular components or prevent host access to these antigens within the graft. The relationship of vascular permeability and integrity to the phenomenon are discussed. The hypothesis is presented that successful heterotransplantation in the cheek pouch of unconditioned hamsters is dependent upon the minimal amount of vascular trauma which accompanies cheek pouch implantation and the maintenance of an intact blood supply during tumor growth.

Some possible mechanisms responsible for the serial transplantability of H. Ad. No. 1 U in cheek pouches of unconditioned hamsters include the above mentioned factors, the protective colloid effect of mucin found in H. Ad. No. 1 U, and the possible antigenic deficiency of this tumor. Evidence suggesting the latter possibility includes the immunologic results reported herein and certain karyologic observations reported by others.

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Supported by research grants CY-4089 and C-4574 from the National Cancer Institute, National Institutes of Health, USPHS.

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