Postoperative active specific immunization in colorectal cancer patients with virus-modified autologous tumor-cell vaccine. First clinical results with tumor-cell vaccines modified with live but avirulent newcastle disease virus

Abstract

Sixteen patients with colorectal carcinoma Dukes' Stage B2, C, or D were treated with an autologous virus-modified tumor-cell vaccine after potential curative tumor resection (R0-Resection). An inoculum of 1 X 10(7) cells incubated with 32 hemagglutination units of nonirradiated Newcastle disease virus (NDV) was given intracutaneously up to four times at 10-day intervals. The delayed-type hypersensitivity (DTH) skin reaction was measured. The vaccination was well tolerated. In 11 of 16 patients an increasing reactivity against the vaccine was observed during the vaccination procedure. A challenge test using autologous tumor cells without NDV after the vaccination cycle revealed a specific antitumor sensibilization in 12 patients. The DTH response was not due to bacterial contamination or sensibility to the virus. Histologic examination of the vaccination site showed a dense infiltration of predominantly helper T-lymphocytes. We conclude that in most of the patients treated active, specific immunization led to a specific antitumor sensitivity.

Human tumor cell modification by virus infection: an efficient and safe way to produce cancer vaccine with pleiotropic immune stimulatory properties when using Newcastle disease virus

“…Toxicity was mild, manifesting as flu-like symptoms and fevers of up to 38°C. [33][34][35] In the majority of treated patients skin responses were observed against the vaccine at the intradermal site of injection. In a significant proportion of patients, synergistic amplifying effects between the two components of the vaccine, ATV and NDV were seen in augmenting local skin reactivity.…”

“…After three vaccinations at 2-week intervals, delayed type hypersensitivity (DTH) responses were increased upon challenge at distant sites with autologous cancer cells (ATV) without the virus. 34,35 This augmented DTH reactivity after ASI treatment upon ATV challenge indicates an augmentation in the precursor frequency of tumor reactive T lymphocytes.…”

Overview of Tumor Cell–Based Vaccines

“…Although many studies demonstrate DTH responses in vaccinated patients, very little immunologic data exists in humans to indicate a potential mechanism for the effectiveness of NDV-infected tumor-cell vaccines. In some patients, T-cell (principally CD4 þ ) infiltrates were seen at the site of vaccination [103], while in another study elevated levels of circulating NK cells were detected in the peripheral blood in response to vaccination [104].…”

Replication-selective viruses for cancer therapy

“…Furthermore, additional mechanisms have been reported to explain virus-induced tumor regression. Viral proteins associated with either tumor cell membrane fragments or intact cells may enhance the immunogenicity of tumor antigens, thereby augmenting host cellular-and humoralmediated destruction of the tumor [7,8,9]. Certain viruses may stimulate host production of cytokines, for example, interferon and tumor necrosis factor-α [10,11].…”