Xenovaccinotherapy for colorectal cancer.
The objectives of this phase I-II trial were to assess the toxicity, immunological and clinical responses induced in 37 patients with stage IV colorectal cancer by the subcutaneous administration of a xenogenic polyantigenic vaccine (XPV) prepared from disrupted murine melanoma (B16) and carcinoma (LLC) cells. An inducing course of vaccinotherapy consisted of 10 immunizations (5 at weekly and 5 at fortnight intervals). Twenty-four hours later each of first 5 vaccinations the patient was subcutaneously given a low dose of the recombinant interleukin-2 (IL-2). A consolidating course of vaccinotherapy consisted of monthly vaccinations. No grade III or IV toxicities, but also laboratory and clinical signs of developing systemic autoimmune disorders were noted in any XPV-treated patient. A significant increase in cell-mediated immunoreactivity to both LLC and B16 antigens (Ags) occurred in the patients after inducing vaccinations, as determined by delayed-type hypersensitivity (DTH) skin reactions, as well as by blood lymphocyte proliferation responses. Vaccinations also led to increased cell-mediated reactivity to murine non-tumor, spleen cell (SC)-associated Ags. This reactivity, however, was not as significant as that to tumor-associated antigens (TAAs). XPV was also found to capable of generating IgG antibody-mediated responses. With immunotherapy concentrations of both interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) detectably elevated in patients' sera, suggesting intensification of T helper 1-/T helper 2-mediated responses in the XPV-treated patients. The average survival of the XPV-treated patients was noticeably superior than was that of the clinically comparable control patients (17 vs 7 months). Collectively the results suggest that xenogenic TAAs are safe to use, able to induce measurable cellular and humoral immune responses, and may be clinically effective in certain colorectal cancer patients.
Seledtsov
Victor I
VI
Department of Cell Biotechnology, Institute of Clinical Immunology, Russian Academy of Medical Science, 14 Yadrintsevskaya Street, 630099 Novosibirsk, Russia. seledtsov@rambler.ru
Niza
Natalya A
NA
Felde
Mariya A
MA
Shishkov
Alexey A
AA
Samarin
Denis M
DM
Seledtsova
Galina V
GV
Seledtsov
Dmitriy V
DV
D000328:Adult; D000368:Aged; D000818:Animals; D000951:Antigens, Neoplasm / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D019496:Cancer Vaccines / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D002277:Carcinoma; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000276:immunology; D004357:Drug Synergism; D005260:Female; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D007074:Immunoglobulin G / Q000187:drug effects / Q000378:metabolism; D007279:Injections, Subcutaneous; D007371:Interferon-gamma / Q000097:blood / Q000187:drug effects; D007376:Interleukin-2 / Q000627:therapeutic use*; D015847:Interleukin-4 / Q000097:blood; D008297:Male; D008545:Melanoma; D051379:Mice; D008875:Middle Aged; D009367:Neoplasm Staging; D016019:Survival Analysis; D018417:Th1 Cells / Q000187:drug effects / Q000378:metabolism; D018418:Th2 Cells / Q000187:drug effects / Q000378:metabolism; D014611:Vaccination
D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D019496:Cancer Vaccines; D007074:Immunoglobulin G; D007376:Interleukin-2; D015847:Interleukin-4; D007371:Interferon-gamma