Immunotherapy of malignant disease: The use of viable sensitized lymphocytes or transfer factor prepared from sensitized lymphocytes

Abstract

Therapeutic studies with cross‐transplant cross‐transfusion were begun in 1966 and have included 56 patients with melanoma, 2 with renal cell carcinoma, 3 with osteogenic sarcoma, 2 with colon cancer, and 1 with synovial sarcoma. Minced fragments of viable tumor were implanted subcutaneously into ABO‐Rh matched pairs with similar tumor on days 1 and 10, followed on the 14th day by 3–10 daily cross‐transfusions of plasma and white blood cells. Subsequently, intradermal implants of viable tumor cells grown in tissue culture have been used, some with added BCG. Complete responses have occurred in 3 patients with melanoma lasting 12, 46, and 51 months; the latter 2 remain alive and well. Partial response occurred in 6 others. Three melanoma patients with a poor prognosis were immunized prophylactically following primary surgical treatment. These 3 developed antibodies (shown by flourescence) against their tumor and remained free of disease—1 for 2 years and 2 for 1 year. Complications have mainly resulted from transfusion incompatibility. Transfer factor is now being used to avoid this problem. Two patients died following the seventh transfusion from complications probably related to treatment.

The role of immunotherapy in the management of patients with malignant melanoma

“…These results are interesting, but the trial is small, and considerably more investigation is needed to establish benefit from transfer factor as an immunotherapeutic agent. Other adjuvant immunotherapy trials of transfer factor were uncontrolled, and results cannot be evaluated [65,66]. Agents including oral BCG and levamisole have been tested as adjuvant therapy, but the data reported are either preliminary or from uncontrolled studies [67,68].…”

“…Nadler and Moore [85] reported 2 longlasting complete regressions of melanoma in 86 patients. Krementz [65] reported responses in 9 of 56 melanoma patients; 3 complete responses lasting from 1 year to over 4 years were noted. Transfusion incompatibilities have been responsible for some patient deaths with this treatment modality.…”

“…In an earlier study, Spitler [86] reported 1 complete regression among 4 melanoma patients treated with transfer factor. In other studies of transfer factor, there was either no benefit or the therapeutic benefit could not be evaluated from the data given [65,[87][88][89]. In another study, patients with disseminated malignant melanoma were treated with xenogeneic immune RNA, but benefit was limited [90].…”

Immunotherapy for Malignant Disease

“…Another approach involves matching patients with the same tumor, se nsitizing them to each other's tumor with su bcutaneous transplants, and then exchanging their leukocytes. Re sponse rates of 15-20% have been reported (50)(51)(52). Thi s is at the price of some se rious transfu sion reactions, si nce allogeneic cells sensitize the patient to HL-A anti gens.…”

“…In an earlier report, Spitler (189) reported one complete regression in fo ur melanoma patients treated with transfer factor (VI). In the other studies with transfer factor, there was either no benefi t or the therapeutic benefi t could not be evaluated from the data given (190)(191)(192)51). In another study (60) , xenogeneic immune RNA was used fo r malignant melanoma, but was of limited benefi t (VI).…”