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[Differences in antitumor effect of various BRMs by intratumoral administration: induction of immunosuppressive
Abstract:
The antitumor effects of biological response modifiers (BRM) in a new experimental mouse model, the "double grafted tumor system", were analysed. BALB/c mice received simultaneous inoculations of Meth-A fibrosarcoma cells on right flank (10(6) cells) and left flank (2 x 10(5) cells) on day 0, and BRMs were injected intratumorally into right tumor on day 3, 4 and 5. The growth of the left-flank tumor was the real target for the evaluation of a given drug after 21 days. PSK (a protein-bound polysaccharide preparation), IL-1 and Cepharanthin, cured not only the right, but also the left, non-treated tumor in a double grafted tumor system. OK-432 (a Streptococcus preparation) and BCG cured the right tumor and inhibited the growth of the left tumor. Lentinan (a polysaccharide preparation) inhibited neither the right nor the left tumor. Immunosuppressive acidic protein (IAP) in serum was increased transiently soon after intradermal injection of PSK, OK-432 and TNF in BALB/c mice. But Lentinan did not induce IAP. IAP in serum was gradually increased after intradermal inoculation of Meth-A tumor in BALB/c mice. At 21 days after tumor inoculation, IAP in serum reached a maximum level (300 micrograms/ml). The serum IAP level of Meth-A-bearing mice as well as that of normal mice increased after the intratumoral injection of PSK. At 21 days after tumor inoculation, IAP in PSK-treated mice returned to normal level. The biochemical differences between PSK-induced IAP (early, inflammatory IAP) and Meth-A-induced IAP (late, tumor-induced IAP) was investigated by crossed immunoaffino electrophoresis (CIAE). Inflammatory IAP was rich in biantennary sugar chain, and tumor-induced IAP was rich in tri-tetraantennary sugar chain.
Insights
Biological response modifiers (BRMs) were tested for antitumor effects using a novel double grafted tumor system in mice. PSK, IL-1, and Cepharanthin showed significant efficacy against both treated and untreated tumors.
Area of Science:
- Immunology
- Pharmacology
- Oncology
Background:
- Biological response modifiers (BRMs) are investigated for their potential in cancer treatment.
- A novel
- double grafted tumor system
- mouse model was developed to evaluate BRM efficacy.
- This model allows assessment of systemic effects on non-injected tumors.
Purpose of the Study:
- To analyze the antitumor effects of various BRMs in a new experimental mouse model.
- To evaluate the systemic activity of BRMs against non-treated tumors.
- To investigate the role of immunosuppressive acidic protein (IAP) in response to BRM treatment and tumor growth.
Main Methods:
- BALB/c mice were inoculated with Meth-A fibrosarcoma cells on both flanks.
- BRMs were injected intratumorally into the right flank tumor.
- Tumor growth inhibition in the left flank (non-treated) tumor was measured after 21 days.
- Serum IAP levels were monitored using crossed immunoaffino electrophoresis (CIAE).
Main Results:
- PSK, IL-1, and Cepharanthin eradicated both right and left flank tumors.
- OK-432 and BCG inhibited the right tumor and suppressed the growth of the left tumor.
- Lentinan showed no significant antitumor effect.
- BRM administration and tumor growth transiently increased serum IAP levels, with distinct biochemical profiles for early (inflammatory) and late (tumor-induced) IAP.
Conclusions:
- PSK, IL-1, and Cepharanthin demonstrate potent systemic antitumor activity in the double grafted tumor model.
- The double grafted tumor system is a valuable tool for evaluating BRMs with potential systemic effects.
- Serum IAP dynamics and biochemical characteristics provide insights into the host's immune response to BRMs and tumor progression.