Abstract

The immunoprophylactic effects of the methanol extraction residue (MER) of BCG were investigated in Strain 2 guinea-pigs injected with cells of the transplantable, diethylnitrosamine-induced, Line 10 hepatocarcinoma. Pretreatment with MER at times ranging from 18 to 182 days prior to tumour implantation protected approximately 40% of guinea-pigs from progressive neoplastic disease. In addition, MER-treated animals developed specific cell-mediated anti-tumour immunity both more rapidly and at higher levels than did non-MER-treated tumour-bearing controls. It was not possible, however, to prognosticate from the results of such laboratory studies to the outcome of immunoprophylaxis.

Highlights

  • methanol extraction residue (MER)-treated animals developed specific cell-mediated anti-tumour immunity both more rapidly and at higher levels than did non-MER -treated tumourbearing controls

  • Previous studies from our laboratory with Strain 2 guinea-pigs obtained from the Weizmann Institute of Science (WI), Rehovot, Israel, indicated that pretreatment with either MER or another sub-cellular fraction of Bacillus Calmette-Guerin (BCG) designated BCG-SS (Minden and Farr, 1969), at times as much as 58 days prior to tumour cell implantation, protected over 400o of guinea-pigs injected with tumour cells from subsequent progressive disease (Minden et al, 1974b)

  • A previous study showed that pretreatment of guinea-pigs with MER as much as 58 days prior to tumour implantation protected a significant proportion of animals from Line 10 metastatic disease

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Summary

MATERIALS AND METHODS

Animals and tumour cells.-Sewall-Wright inbred Strain 2 guinea-pigs were obtained from the breeding colonies of the Weizmann. Strain 2 male and female guinea-pigs were covered by migrating cells were magnified on injected i.d. with MER (0 5-1 0 mg in 041 ml to paper by projection microscopy and isotonic saline) into the left flank at times up measured by planimetry (Jokipii and Jokipii, to 182 days prior to the contralateral inocu- 1974). Soluble tissue fraction purified by Ficoll-Isopaque gradient components wAere prepared by 3M KCI centrifugation (Boyum, 1968) This fraction, extraction from both ascites-grown Line 1]0 which consisted largely of lymphocytes, was tumour cells (SA-10) and from perfused collected by aspiration, washed twice by normal adult liver tissue (SA-N) by a modification of the procedure of Meltzer et al. Cultures containing 1 ml of cell suspension in (17 x 100) mm tubes protein per test) in both MER-treated and were incubated in the presence or absence of control tumour-cell-injected guinea-pigs. WEISS thymidine (1 ,uCi/tube; New England Nuclear, Boston, Mass.) was added to the culture tubes for the final 16 h of incubation, following which the samples were processed by trichloroacetic acid precipitation on to filter pads and the amount of incorporated radioactivity determined

RESULTS
Delayed cutaneous hypersensitivity studies in MER-pretreated animals
Mlacrophage migration inhibition studies
Lymphocyte stimulation
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