G. Mark Kollmorgen

Evaluation of time and dose in treating mammary adenocarcinoma with immunostimulants.

SummaryBCG, C. parvum, and reovirus were used as immunostimulants in treating murine mammary adenocarcinoma (A-10) after tumor burden had been minimized with BCNU. Immunostimulants were administered at different times with respect to chemotherapy. Different doses were used to determine the optimal response as measured by survival. BCG induced the best response when 6.67×105 organisms were given 2 days after chemotherapy. The optimal response with C. parvum was observed after a dose of 0.35 mg was given 1 or 2 days after chemotherapy. Similarly, reovirus produced the best response when 1010 plaque-forming units were given 2 days after chemotherapy. These data are consistent with previous findings and support the notion that immunostimulants require an appropriate lymphoid substrate in order to induce an adequate anti-tumor response.

Adherent indomethacin-sensitive suppressor cells in malignant melanoma - Correlation with clinical status

SummaryTwenty-five patients with malignant melanoma were studied to determine the mechanisms underlying decreased cellular immunity in this disease. Sixteen patients were examined following surgical resections of tumor, and nine patients had evidence of metastases. Patients with metastatic disease (group II) had decreased lymphocyte transformation to concanavalin A (48,255±30,074) compared with controls (83,550±41,277) and patients free of disease (group I) 110,231±59,990) (P>0.01). Rigorous depletion of monocytes by adherent techniques resulted in an improvement in blastogenesis in seven of nine group II patients, whereas controls and group I patients had marked decreases in reactivity. Indomethacin also improved lymphocyte reactivity; a mean of 166.4% was recorded in five metastatic disease patients studied, as against a mean of 2% in group I and 9.65% in controls. In seven patients followed serially the presence of adherent suppressor cells tended to correlate with progressive disease, shorter survival, and decreased skin test reactivity.

Immunotherapy of EL4 lymphoma with reovirus

SummaryEL4 lymphoma was grown as an ascitic tumor in the peritoneal cavity of C57Bl/6 mice. Animals with different tumor burdens (either 107 or 109 cells) were treated with a single intraperitoneal injection of BCNU using doses from 20–40 mg/kg. Response as measured by mean survival time and percent survival was dependent on tumor burden and dose of drug. The objective of chemotherapy was to increase the mean survival time, but not the percent survival, in order to evaluate the therapeutic effect of reovirus. Mice were given 108, 109, or 1010 Pfu of reovirus at various times with respect to chemotherapy. The number of mice cured after treatment with both BCNU and reovirus was significantly greater compared to mice treated with BCNU only. Mice cured with combination therapy developed tumor-specific immunity as measured by cytotoxic lymphocytes and serum, and resistance to a lethal tumor challenge.

Inhibition of lymphocyte response by prostaglandin-producing suppressor cells in patients with melanoma

Peripheral blood mononuclear cells (PBMC) from 11 patients with metastatic melanoma (group II) had a significant decrease in blastogenesis to concanavalin A (Con A) (38.7±7.7 cpm × 103; mean ± SE) compared to 21 patients who were disease free (70.6±6.7) or 16 healthy controls (83.6±10.3). If PBMC from patients were preincubated for 72 hr prior to exposure to mitogen, blastogenesis was restored to normal. In group II patients a similar improvement in reactivity of fresh PBMC occurred with indomethacin addition or following rigorous depletion of adherent monocytes. Supernatants from cells cultured with and without Con A in several group II patients contained very high levels of endogenous PGE2. Patients had a greater percentage of T lymphocytes bearing Fc receptors for ox erythrocytes (Tγ) than controls, which appeared to correlate with the increased sensitivity to suppression by exogenously added PGE2. These data suggest that the decreased blastogenesis in certain melanoma patients is due to an increase in PGE2 production by monocytes, along with an increase in lymphocyte sensitivity to its effects.

Histologic evaluation of L1210 leukemia in treated and untreated mice

SummaryBDF1 mice bearing L1210 leukemia were treated with chemotherapy or in combination with neuraminidase-treated cells and BCG. Histological evaluation was done on these mice at various intervals after therapy in order to determine the rate and extent of metastatic involvement in various tissues and organs. Results were compared to tumor-bearing mice which were not treated. In all animals, tissues were classed as having minimal involvement, moderate involvement or maximal involvement based on a scale of 0 through 4. Results indicated that: (a) mice which were long term survivors did not completely reject their tumor for weeks after treatment with chemotherapy and immunotherapy; (b) complete tumor rejection did not indicate a restoration of normal tissue integrity; and (c) failure of chemotherapy-immunotherapy had no consistent pathology, but was probably due to tumor distribution rather then tumor burden per se.