Immunotherapy With Whole Cell Vaccines
The following information is summarized in a table located at the end of this section.
Most clinical studies of NDV-infected, whole cell vaccines that have been reported in scientific literature were conducted in Germany.[15,16,17,18,19,20,21,22,23,24,25,26,27,31,32] However, the largest reported trial was performed in China. Reviewed in [14,34,35,36] Most of these studies involved patients with colorectal cancer,[15,16,19,20,22,33] breast cancer,[17,18,25] ovarian cancer,[17,18,23] renal cell cancer,[21,26] or malignant glioma. The nonlytic strain NDV Ulster was used to prepare autologous tumor cell vaccines in all of the studies.
Data from a 2004 pilot clinical trial of an NDV-modified autologous tumor vaccine in 20 patients with stage III or IV head and neck squamous cell carcinomas suggest that the vaccine strategy can stimulate human antitumor immune responses in a manner similar to those found in animal models and may significantly prolong 5-year survival rates in this patient population. The study demonstrated the feasibility and safety of the vaccine regimen, and no major side effects were observed in any of the patients.
The use of NDV-infected, whole cell vaccines in patients with either locally advanced or metastatic colorectal carcinoma was examined in one phase I clinical trial and two phase II clinical trials.[15,16,19,20,22] The phase I trial helped establish the optimum number of tumor cells and the optimum amount of virus to use in the average patient to produce the best possible immune response. Immune responses were monitored by means of a skin test that measured the extent of inflammation and hardening of the skin at vaccination sites (i.e., delayed-type hypersensitivity responses). The exact number of patients treated in this trial cannot be determined because nonidentical patient populations were described in the two published study reports.[19,20] One report lists 16 patients: 2 with stage II disease, 4 with stage III disease, and 10 with stage IV disease. The second report lists 20 patients: 12 with stage II disease and 8 with stage III disease. It is also not clear whether findings from individual patients were reported twice (i.e., in both trial reports). Patients with metastatic disease were allowed to enter this trial only if they had a solitary metastatic tumor.
In the trial, NDV-infected, autologous whole cell vaccines were administered to patients by intradermal injection beginning 4 weeks after surgery to remove the primary tumor or the metastatic tumor. Each patient received a total of 5 vaccinations, 4 given at 10-day intervals and a final booster given approximately 23 weeks after surgery. One of the study reports  states that 75% of the patients (12 of 16) showed increased immune system reactivity against uninfected, autologous tumor cells during the vaccination program. These responses were monitored by injecting uninfected, irradiated tumor cells into the skin and looking for delayed-type hypersensitivity responses. Histologic examination of several vaccination sites during the trial showed the presence of infiltrating immune system cells. These infiltrating cells were composed primarily of helper T cells; some cytotoxic T cells were also present, but B cells (i.e., antibody-producing cells) were either scarce or absent.