A mouse model for immunotherapy of osteosarcoma

Abstract

Various combinations of the prostaglandins synthetase inhibitors, aspirin or indomethacin, and Corynebacterium parvum were used as adjunctive therapy to surgery in the treatment of the metastasizing Dunn osteosarcoma C3H/HeJ mice. In doses corresponding to those that could be tolerated by humans all three agents given singly reduced the number and estimated weight of metastases whether they were administered pre-operatively or post-operatively. When the two modalities of therapy were combined a significant additive anti-tumour effect was observed with both C. parvum and aspirin and C. parvum and indomethacin, but only if treatment was commenced pre-operatively. Similar results were obtained with two other metastasizing turnouts, viz. the B16 melanoma and the Lewis lung carcinoma. In the absence of any evidence for an interaction between the prostaglandin synthetase inhibitors and circulating tumour cells, it was felt that the additive effect could be best explained in terms of interference with prostaglandin-mediated negative feedback of the anti-tumour action of C. parvum. C. parvum 0.025 mg Aspirin 100 mg/kg b.d. C. parvum + aspann C. parvum 0.1 mg Aspirin 100 mg/kg b.d. C. parvum + aspirin C. parvum 0.025 mg Aspirin 100 mg/kg b.d. C. parvum + aspinn C. parvum 0.1 mg Aspirin 100 mg/kg b.d. C. parvum + aspmn C. parvum 0.025 mg Aspirin 100 mg/kg b.d. C. parvum + aspinn C. parvum 0.025 mg Aspirin 100 mg/kg b.d. C. parvum + aspmn

Phenotypic identification of suppressor‐effector, suppressor‐amplifier and suppressor‐inducer T cells of B cell differentiation in man

“…The data in Table 1 demonstrate that AMLR-activated CD8+,Leu 8-cells are capable of suppressing the development of antibody-forming cells in the absence of fresh CD8+ T cells, whereas similarly activated CD8+,Leu 8' cells require fresh CD8' cells to exert their suppressive effect. Since recent experiments have shown that the target of suppression is the helper (CD4+,Leu8-) T cell rather than B cells [9], we interpret our results as indicating that CD8+,Leu 8cells exert their inhibitory effect directly on the CD4+,Leu 8helper cell without the concomitant action of any other cell type. In contrast to CD8+,Leu8-cells, CD8+,Leu 8' cells require the presence of fresh CD8' cells to exert any suppressive effect.…”

The Influence of Paramunisation, Tumor Cell Vaccination and Whole Body Irradiation on the Growth of Radiation‐induced Murine Osteosarcoma

“…Exp 1,5,6,7;. Tables 5,6) and was relatively constant except for three experiments where the TD,, was five times higher (2.5 x 104 cells) (Table 4, Exp.…”

“…It has been demonstrated that osteosarcoma in mice can serve as a suitable model for the disease in man (7, 9). The most important similarities between human and murine osteosarcomas are their low antigenicity and their metastasizing capacity (1,7,9,15,23,24,27). Forms of therapy which modulate host defence mechanisms, such as treatment with sarcoma cell vaccines, BCG, Corynebacterium parvum, Brucella abortus extracts and interferons have been shown to prevent the growth of osteosarcoma cells and the establishment of lung metastases to some extent in mice (3, 4, 8,9,11,22,25).…”