Chester M. Southam

Vaccine trials for osteogenic sarcoma. A preliminary report.

nous vaccine prepared from the primary tumor tissue was given to a child with osteogenic sarcoma and pulmonary me tastases. During the 15 day course of in jections the child gained seven pounds; following treatment the disease pro gressed and the patient died. However, the temporary improvement suggested that immunotherapy may have inhibited tumor growth. A formal controlled trial of immunotherapy in less advanced dis ease was begun in April, 1966. Patients under the age of 25 with osteogenic sar coma of the long bones but no evidence of spread beyond the primary site and who had been treated by amputation were included in the study. The auto genous vaccine was given in the post operative period following amputation. If metastases (usually pulmonary) ap peared the vaccine was judged a failure.

Growth of human cancer cells in interscapular brown fat of rats.

Macroscopic growth of human cancer cell lines J-111 and RPMI-41 occurred frequently in the interscapular brown fat pad (as well as in lungs and certain other organs) following i.v. inoculation into newborn rats. Tumor growth in this tissue of rats has not been observed previously, to our knowledge, with cither spontaneous or transplanted tumors. HEp 2 cells rarely grew in the fat pad, although they did grow well in lungs and adrenals. Consideration of the anatomical and physiological characteristics of the interscapular fat pad suggests that the local tissue milieu has a greater influence than vascular anatomy on the deposition and growth of the tumor cells in this structure.

SELECTIVE TISSUE LOCALIZATION OF HUMAN CANCER TRANSPLANTS IN NEWBORN RATS

SUMMARY Newborn rats were inoculated via the umbilical vein with suspensions of tissue-cultured cell lines of human cancer (HEp 2 and J-111). Fluorescent antibody studies demonstrated that many of these cells were deposited in the liver, but they seldom grew to produce tumor nodules in the liver. When they did grow in liver (1/11 rats with HEp 2 and 4/16 with J-111), implants also grew in the lungs. This is in contrast to results of transplantation of these cells into newborn rats via the tail vein, which produced progressively growing tumors in the lungs and adrenals of a great majority of the recipients, and never produced implants in the livers. The observations are interpreted as indicating a role of local tissue factors in determining receptivity to the growth of tumor cell implants. The observations provide experimental evidence in support of the concept that distribution of tumor metastases may be due in part to differences in the susceptibility of various tissues for the growth of randomly distributed cancer cells.

Cataracts in Bleomycin-Treated Rats

Bleomycin was administered to 126 normal or human-tumor-bearing baby rats we observed for the development of cataracts. Eighty-four percent of the rats receiving this drug before the age of 10 days developed lens opacities. Bleomycin given to 10-day-old rats or older did not induce cataract formation. The cataracts initially occurred in the nuclear area and later involved most of the lens whether or not bleomycin was later discontinued. The presence of the tunica vasculosa lentis in rats younger than 10 days old may explain why cataracts developed only in these young animals.

SPECIFIC ADOPTIVE AND PASSIVE IMMUNOTHERAPY BY PARABIOSIS FOR SYNGENEIC MOUSE AND RAT TUMORS

A laboratory model of cancer that is suitable for immunotherapy studies, and that simulates the conditions encountered in clinical oncology, requires experimental animals that either have progressively growing autochthonous or syngeneic primary tumors or have had such tumors treated by methods that leave a residuum of local or metastatic tumor cells. In the studies of adoptive and passive imrnunotherapy summarized here, we utilized both of these tumor situations. Of the numerous methods that can be used for immunotherapy, the various methods of transferring cellular immunity are of particular interest to oncologists because of the many indications that cell-mediated immunity plays a major role in specific immunologic resistance to tumor growth. In clinical medicine, the technique of plasmapheresis permits the frequent transfer of large numbers of lymphoid cells. This technique has not been scaled down for application to small laboratory animals, but a similar massive and sustained transfer of leukocytes (and serum) can be achieved by parabiosis. By using syngeneic animals as “donors,” the immunity that is transferred to the “patients” can be tumor specific. Of course, this technique provides a combination of adoptive and passive immunotherapy: it does not permit dissection of mechanisms; the result is the sum of the effects of all mechanisms that affect the tumor. Further details of these studies will be published elsewhere.’-:’

Growth of Human Cancer Cells as Lung Metastases in Immunologically Tolerant Rats

Summary Newborn rats were made tolerant to human cell antigens by intravenous injection of Amnion B cells, a permanent human cell line of normal origin. At various intervals thereafter each animal, and non-tolerant litter mate controls were challenged by SC and IV injections of the malignant human cell line J-111. Tumor nodules of J-111 cells grew SC and in the lungs of most of the tolerant rats challenged at ages from 7 to 14 days, but not in their controls. Challenge at age 19 days produced SC tumors but there was no growth from the IV inoculum.