Eliyahu Yarkoni

Immunotherapy of a guinea pig hepatoma with ultrasonically prepared mycobacterial vaccines

SummaryOil-in-water emulsions containing either mycobacterial cell walls (CW) or killed whole cells attached to the oil droplets were prepared by ultrasonication and by a modified grinding procedure. The immunotherapeutic potency of the ultrasonically prepared vaccines was at least as great as that of similar vaccines prepared by emulsification in a tissue grinder. Among the advantages of ultrasonication over grinding for the preparation of mycobacterial cell and cell wall vaccines are simplicity and the ease with which sterility may be maintained. Both the ultrasonic and modified grinding methods are less time-consuming than published procedures for preparing mycobacterial vaccines.

Efficacy of mycobacterial components in the immunotherapy of mice with pulmonary tumor deposits

SummaryThe effectiveness of each of two mycobacterial components and a synthetic analog of one of them in the eradication of pulmonary deposits of intravenously injected syngeneic fibrosarcoma 1023 in C3H mice was studied. BCG cell walls (BCG CW), trehalose 6,6′-dimycolate (TDM) or 6,6′-di-0-2-tetradecyl, 3-hydroxyoctadecanoyl-α,α-trehalose (C76), a synthetic analog of TDM, was administered in emulsified form by three different routes: intraperitoneal, intradermal, or intravenous, 24 h after intravenous injection of 1023 tumor cells. The most effective form of therapy was TDM given by the intraperitoneal route; about 50% of treated animals were cured. Higher doses of BCG CW or C76 also led to a significant number of cures. Each agent caused a significant prolongation of survival time of the treated mice at two or more of the dosages tested; however, their routes of optimal activity varied.

Immunotherapy of a guinea pig hepatoma with vaccines containing mycobacterial fractions

SummaryBCG cell walls (CW) were compared to trehalose-6,6′-dimycolate (TDM) in admixture with endotoxin (ET) for their potency to cause regression of a transplanted guinea pig hepatoma. On a weight basis, CW were at least as active as ET-TDM. Toxicity of ET and of ET-TDM were greater than that of CW as judged by weight loss after intravenous administration to normal guinea pigs.

Active specific immunotherapy of guinea pigs with visceral tumor implants

SummaryGuinea pigs, each with established, 7-day-old, syngeneic visceral micrometastases of line 10 tumor implanted intravenously, were immunized by intradermal inoculations into several sites of a mixture of irradiated line 10 cells and an emulsion containing heat-killed BCG or Mycobacterium phlei bacilli. This treatment led to survival of 72 of 80 treated animals (90%). Therapeutic effectiveness depended on the dose of mycobacteria and on that of irradiated tumor cells. Animals treated by intradermal injection of mycobacteria attached to oil droplets alone or with irradiated tumor cells alone, all died with multiple foci of pulmonary tumor.

Treatment of mice with lung metastasis from a dermally implanted fibrosarcoma: comparison of intratumoral trehalose-6,6'-dimycolate (cord factor) and surgery.

Abstract Intralesional administration of emulsified trehalose- 6,6′ -dimycolate was compared to surgery in the treatment of mice with growing intradermal implants of a syngeneic fibrosarcoma. Treatments were given about one month after tumor implantation when a majority of animals so treated had metastatic foci of tumor in the lungs. Mice treated with trehalose- 6,6′ -dimycolate or by surgery survived significantly longer than untreated mice. Some treated mice were alive and tumor-free six months after tumor inoculation. The differences in cure rates and prolongation of survival between the trehalose- 6,6′ -dimycolate treated group and the surgically treated group were not statistically significant. Several mice died soon after surgery; no deaths could be attributed to the acute effects of immunotherapy.

Resistance to tumor growth in guinea pigs immunized with lyophilized tumor cells

SummaryLiving BCG, killed Mycobacterium tuberculosis cells, or BCG cell walls (CW) augmented the immunogenicity of lyophilized syngeneic ascites hepatoma (line 10) of strain-2 guinea pigs. Effective vaccine contained living BCG and lyophilized line-10 cells, or mycobacterial cells or CW attached to oil droplets and lyophilized line-10 cells. Protection against the challenge tumor was evident 14 or 21 days after one administration of either vaccine.

Immunotherapy of Guinea Pigs with a Transplanted Hepatoma: Comparison of Intralesionally Injected Emulsions Containing Heat-Killed Nocardia rubra, Mycobacterium bovis (BCG) and Mycobacterium phlei

Heat-killed cells of Mycobacterium bovis (BCG), Mycobacterium phlei and Nocardia rubra were each tested in emulsified form for their ability to cause regression of established dermal transplants and lymph node metastases of a syngeneic hepatocarcinoma in guinea pigs. On a weight basis, BCG was superior to N. rubra in causing tumor regression. Under the conditions tested N. rubra was inferior to M. phlei in its antitumor activity. M. phlei and BCG were approximately the same in their therapeutic potency. In BCG-sensitized guinea pigs, N. rubra provoked a weaker delayed cutaneous hypersensitivity (DCH) reaction than did BCG. In N. rubra-sensitized guinea pigs, BCG provoked a weaker DCH reaction than did N. rubra. Purified protein derivative of M. tuberculosis was more active in eliciting DCH in BCG-sensitized guinea pigs than in animals sensitized with N. rubra.

A specific vaccine effective against stage I and stage II malignant disease in guinea pigs effect of variations in preparations and storage

SummaryGuinea pigs, each with an established, syngeneic dermal line 10 tumor and lymph node metastases, were immunized by intradermal injection of a mixture of irradiated line 10 cells and an emulsion containing heat-killed BCG. Immunization eradicated 7- or 10-day-old dermal tumors (about 10 or 12 mm in diameter, respectively) and prevented growth of microscopic lymph node metastases. Fourteen-day-old dermal tumors (about 15 mm in diameter) were not rejected by immunization.Guinea pigs with stage II disease (21-day-old dermal tumors and palpable metastases in the first draining lymph node) were treated by excision of the dermal tumor and the first draining lymph node, and by specific immunization. This treatment eliminated tumor cells remaining in the second draining lymph nodes. The surgical treatment alone was not curative, palpable metastases in the second draining lymph nodes progressed and the animals died (some with visible lung metastases).Emulsions containing killed BCG were good adjuvants even after prolonged storage at 4° C, but lost most of their adjuvant activity after autoclaving or freezing.