Over the last four years a guinea pig model of active‐specific immunotherapy (ASI) with a syngeneic tumor celhbacillus calmette‐Guerin (BCG) vaccine was translated into a prospectively randomized, controlled clinical trial in patients with colorectal cancer. Primary tumors from patients undergoing standard surgical resection were dissociated enzymatically and cryopreserved by techniques that maintain cell viability. Patients with transmural extension of tumor or nodal metastases were randomized into groups treated by resection alone (control) or resection plus ASI. With a mean follow‐up of 28 months (range, 14–24), only 3 of 20 treatment patients had recurrences and none have died, whereas 9 of 20 control patients had recurrences and 4 died. These differences are statistically significant and are sufficiently encouraging to warrant expansion of these studies into other research centers. Cancer 55:1236‐1243, 1985.
A vaccine of Bacillus Calmette-Guérin (BCG) admixed with tumor cells induced systemic immunity and had a therapeutic effect on subclinical, disseminated micrometastases. Inbred strain 2 guinea pigs given intravenous injections of either 10(4), 10(5) or 10(6) syngeneic L10 hepatocarcinoma cells were vaccinated after metastatic foci were established in the lung parenchyma. The studies demonstrate that under defined conditions of vaccine preparation and regimen, nontumorigenic preparations of BCG and tumor cells can cure the majority of animals of otherwise lethal visceral metastases. Histopathologically it was determined that immunization with these vaccines prevented the progressive growth of pulmonary micrometastatic foci approximately 0.1 mm in diameter. However, in this micrometastasis therapy model, the number of metastatic tumor foci is a major limitation in the efficacy of vaccine therapy. No protection against L10 tumor was achieved when antigenically distinct but syngeneic L1 hepatocarcinoma was used in the vaccine, suggesting that this is a tumor-specific immunotherapeutic procedure. This BCG-L10 tumor vaccine was also effective in curing guinea pigs of minimal disseminated tumor burden when administered after surgery of an established skin tumor and draining lymph node.
An alpha macroglobulin fraction (19S) was isolated from the serum of rats and BC(3)F(1) mice by zonal ultracentrifugation. Both the isologous and heterologous macroglobulin fractions increased survival among BC(3)F(1) mice x-irradiated with 750 roentgens. The mouse macroglobulin fraction also enhanced radiation recovery of hematopoietic tissue as measured by colony-forming assay and iron-59 incorporation into erythropoietic cells. The overall difference in hematopoietic activity in the irradiated (400 roentgens) mice treated with the macroglobulin fraction, in comparison with this activity in the controls, was three- to fivefold in the bone marrow and nine- to tenfold in the spleen between days 4 and 7 after irradiation. This effect was not obtained with the isologous serum protein fraction containing proteins of smaller molecular weight.
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