Craig S. McCune

Renal cell carcinoma treated by vaccines for active specific immunotherapy : correlation of survival with skin testing by autologous tumor cells

SummaryEighteen patients with metastatic renal cell carcinoma, who were treated by vaccines for active specific immunotherapy, also completed skin testing with autologous tumor cells, both prior to and following vaccine treatment. All patients have now been followed for more than 5 years. Ten patients who remained skin-test-negative following treatment had no clinical responses, and all had expired by 22 months. Eight patients became skin-test-positive; three of these had clinical regressions and three remain alive after more than 69 months. The survival times of the skin-test-positive group were significantly superior to those of the skin-test-negative group. The results suggest that skin testing with autologous tumor cells may accurately identify those patients who have acquired antigenspecific cell-mediated antitumor immunity.

Specific immunotherapy of advanced renal carcinoma: Evidence for the polyclonality of metastases

Autologous, irradiated (10,000 rads) tumor cells mixed with C. parvumwere given weekly to 14 patients with metastatic renal carcinoma. The tumor tissue had been cryopreserved with DMSO. No significant toxicity was produced. Four patients underwent objective responses, and a fifth had prolonged stabilization (27+ months). Varying responses occurred simultaneously in different metastatic lesions within the same patient. Responding patients usually had an excellent ambulatory status and received greater than 20 × 107tumor cells.

Treatment of metastatic breast cancer with aminoglutethimide

Seventy‐three women with metastatic breast cancer were treated with aminoglutethimide and dexamethasone. No complete responses occurred. Ten patients (16%) achieved partial responses (mean duration, 12 months). The proportions of patients responding by disease site were breast (50%), nodes (33%), skin (23%), bone (16%), lung (11%), and liver (7%). Response did not correlate with age, menopausal status, performance status, or cortisol suppression. Ninety percent of responders had had previous responses to hormonal manipulations. No responses occurred in estrogen receptor negative patients. An additional 20% of patients had disease stabilization of eight or more months (mean, 17 months). Severe bone pain was present in 47 patients and was relieved in 19. Side effects occurred in 75% but caused discontinuation of therapy in only four patients. Somnolence, nausea, rash, Cushings syndrome, and leukopenia were the most frequent side effects. Aminoglutethimide with dexamethasone is an effective hormonal treatment for metastatic breast cancer.

Active specific immunotherapy for metastatic colorectal carcinoma : Phase I study of an allogeneic cell vaccine plus low-dose interleukin-1α

A vaccine consisting of four allogeneic colon carcinoma cell lines (DLD-1, HCT116, WiDr, and T84) mixed with the adjuvant DETOX (Mycobacterium phlei cell wall and Salmonella minnesota lipid A) was administered to 25 patients with low-volume metastatic colorectal carcinoma. The first eight patients received vaccine only, given intradermally on three occasions at 3-week intervals. Subsequent patients also received subcutaneous interleukin-1 alpha (IL-1 alpha), 0.3-0.5 microgram/m2 per day for 8 days after each vaccination in an outpatient setting. Vaccine alone caused local erythema, induration, and pruritus. IL-1 caused fevers, chills, and rigors that started in 4 h and lasted 1-2 h. One patient developed a brief loss of consciousness with a rigor that resolved without sequelae. One episode of mild hypotension occurred. Fatigue occurred by day 8 of IL-1. A substantial increase in the number of patients with positive skin tests to DLD-1 and HCT116 occurred after vaccine treatment both without and with IL-1 alpha. An allogeneic cell vaccine plus subcutaneous IL-1 was administered safely to outpatients with some evidence of in vivo effect observed.

A study of aminoglutethemide and hydrocortisone in patients with advanced and refractory prostate carcinoma

We have studied aminoglutethemide (AG) combined with hydrocortisone in 28 patients with advanced and refractory prostate carcinoma. All the patients had failed at least one endocrine therapy. Six patients received only one prior hormonal treatment. Five patients were off study within 3 weeks due to early death and toxicity, 14 had progressive disease, and 9 had stable disease. No objective partial remission was observed, but the nine stable patients had therapeutic benefit, with improvement in bone pain and performance status for a median duration of 153 days. Three patients withdrew because of postural hypotension, dizziness, weakness, and lethargy. The median survival of the entire group was 186 days (range 41–606 days). Our results suggest that aminoglutethemide and hydrocortisone can be an alternative treatment for patients with advanced and refractory prostate carcinoma.

Active specific immunotherapy with tumor cells and Corynebacterium parvum: a phase I study.

Autologous, irradiated (10,000 rads) tumor cells mixed with C. parvum were given as weekly intracutaneous injections to fifteen patients with residual malignant disease. The toxicity was minimal and distinctly less than has been seen with tumor cell‐BCG immunotherapy. A goal of 4 injections of 107 cells each was possible in only 4 patients because of limitations in methods of disaggregation and quantity of tumor available. The feasibility aspects are discussed and a case report of a prolonged regression is presented.

Somatic cell hybridization of human tumor samples.

Human intraspecific hybrids were formed between tumor cells isolated from both primary and metastatic tumors and a tissue culture adapted cell line, D98OR, a HeLa derivative which is thioguanine and ouabain resistant. Five different tumor types in all were attempted: renal cell carcinoma, colon adenocarcinoma, melanoma, chrondrosarcoma, and hepatocarcinoma. The tumor tissue was either (1) immediately dissociated and fused, or (2) frozen and later thawed, dissociated, and fused. Two different PEG concentrations were used. The results reported here demonstrate that: (1) hybrid tumor cell lines can be made from several types of cancer, (2) unfrozen tumor tissue fused with D98OR by exposure to 50% PEG appears optimal, (3) chromosome loss, as determined by flow cytometry studies of hybrid DNA content, is minimal, and (4) hybrids have characteristics consistent with derivation from tumor cells rather than derivation from the nonmalignant cells of a tumor.