Irradiated Tumor Cell Vaccine Research Articles

Increased Immunogenicity of a Spontaneous Variant Clone of the 13762A Rat Mammary Adenocarcinoma<xref ref-type="fn" rid="FN2">2</xref>

The 13762A rat mammary adenocarcinoma is weakly immunogenic and spontaneously metastasizes to regional lymph nodes and lungs. A clone (18A) was isolated from the parental tumor, which grew for 3 weeks in normal F344 rats, forming tumors up to 2-3 cm and some nodal metastases, and then completely regressed. Pretreatment of recipient rats with 450 rad permitted progressive growth and death due to metastases. The behavior of 18A has been stable during a period of 120 days in continuous culture or for 6 in vivo passages in irradiated rats. Regression of 18A was associated with intense tumor mononuclear leukocytic infiltration, whereas parental tumors of the same size recruited few leukocytes. Regressions occurred when 18A cells were placed intradermally, sc, or im, but iv injections were not rejected. Parental tumors grew progressively at all sites. Regressor rats were specifically immune to challenge with both 18A and parental tumor but not to an unrelated mammary carcinoma (R3230AC). Irradiated 18A tumor cell vaccines protected recipients against challenge with parental tumor, but similar vaccines of irradiated parental tumor cells were ineffective. The systemic adoptive transfer of immune lymphocytes more strongly inhibited the growth of established (7 days) 18A than parental tumor. It was concluded that the parental 13762A tumor contained stable variants that were significantly more immunogenic and more susceptible to immune attack than the parental tumor. Such variant tumor lines may be useful in the study of the host response to metastasis.

Active specific immunotherapy of murine leukemia. I. Irradiated tumor cell vaccine.

This report describes a new animal model for active, specific, systemic immunotherapy of leukemia. Mice were challenged (day 0) with 10(3) viable LSTRA cells and treated later with a vaccine containing 10(7) irradiated LSTRA cells. Four intraperitoneal or intravenous vaccine injections, on days 2, 9, 16 and 23, caused significant prolongation of survival; single injections by the same routes had inconsistent effects. Vaccine was not effective against a higher initial challenge dose, when given later in the course of tumor growth, when given intradermally or when used in weanling mice. The therapeutic effect was specific since a vaccine composed of an antigenically unrelated leukemia was ineffective. These results suggest that LSTRA is suitable for studying active, systemic, specific immunotherapy.

Progression of the immune response to solubilized tumor antigens.

Local adoptive transfer assays (LATA) were used to analyze and compare the progression of the immune response in C3H/HeJ mice to irradiated tumor cell vaccine and to crude 3M KCl solubilized antigens extracted from a syngeneic methylcholanthrene-induced fibrosarcoma. Sequential LATA performed 2, 6, 9, 12 and 15 days after soluble antigen pretreatment of spleen cell donors revealed a sinusoidal evolution of lymphoid cell activity. An initial brief period of potent tumor facilitation (days 6-9) was followed by a phase of tumor neutralization (days 9-12) which decayed by day 15. On the other hand, spleen cells from donors sensitized with irradiated tumor cells exhibited consistent tumor neutralization which was sustained throughout 15 days. Thus the tumor growth facilitation observed only in CSA-treated donors may represent a qualitative difference in the immune state induced by soluble, as opposed to cellular, forms of tumor antigen.

Immunology and Adjuvant Chemoimmunotherapy of Breast Cancer

Antibody against a breast carcinoma antigen was present in patients with breast carcinoma and other cancer more often (P less than .05) than in normal women. The incidence of antibody in women with breast carcinoma correlated with the presence or absence of gross tumor, and the titer of antibody paralleled the clinical course. These results suggest importance of a host-immune response to breast carcinoma. Fifty-seven patients with stage II carcinoma of the breast were entered into a prospective randomized adjuvant chemoimmunotherapy program of cyclophosphamide, methotrexate, and fluorouracil, and BCG vaccine +/- an irradiated allogeneic tumor cell vaccine. After 24 months of study, metastases occurred in two patients (3.5%) and a new primary carcinoma developed in the contralateral breast in two others, for an overall treatment failure rate of 7%. Adjuvant chemoimmunotherapy can delay early recurrence. Long-term follow-up is needed to assess the significance of these results.