Human / Clinical Studies
In two of the above-mentioned studies, the phase I colorectal cancer study [19,20] and the phase II ovarian cancer study, histologic examination of several vaccination sites revealed the presence of infiltrating immune system cells. These infiltrating cells, however, consisted primarily of helper T cells (CD4 antigen-positive cells); cytotoxic T cells (CD8 antigen-positive cells) were present, but only as a minor component. In another study, vaccination sites from five cancer patients (two with colon cancer, two with melanoma, and one with ovarian cancer) also contained infiltrates of predominantly helper T cells. In fact, CD8 antigen-positive T cells could not be detected in the lymphocytes cultured from vaccination sites of two of these five patients. Reviewed in  The presence of small numbers of cytotoxic T cells at vaccination sites may be an important factor to consider when evaluating the results of the whole cell vaccine trials because animal studies [54,55,56,57] Reviewed in [16,19,58,59,60,61,62,63,64,65,66] and human studies  have suggested that this class of T cells is required for effective, long-term anticancer immunity. It should also be noted that, in another study, increases in NK cell activity were measured in blood samples from two patients with colorectal cancer who exhibited delayed-type hypersensitivity responses at vaccination sites, but cytotoxic T cells directed against tumor-specific antigens could not be detected. Overall, these results indicate that NDV-infected, autologous, whole cell vaccines may be able to stimulate NK cell activity, which may have contributed the clinical outcomes described above, but also that these vaccines may be ineffective in promoting at least one additional immune system response (i.e., the production of tumor-specific antigen-targeted cytotoxic T cells) thought to be important to establishing long-term anticancer immunity. Whether the inclusion of bispecific monoclonal antibodies (refer to the Laboratory/Animal/Preclinical Studies section of this summary for more information) in the whole cell vaccines will make them more effective remains to be determined.
Table 3. Studies of NDV-Infected Tumor Cell Vaccines in Which Therapeutic Benefit Was Assesseda
No. = number; wk = week.
a See text and the NCI Dictionary of Cancer Terms for additional information and definition of terms.
b Number of patients treated plus number of patients control may not equal number of patients enrolled; number of patients enrolled = number of patients initially recruited/considered by the researchers who conducted a study; number of patients treated = number of enrolled patients who were given the treatment being studied AND for whom results were reported; historical control subjects are not included in number of patients enrolled.
c The strongest evidence reported that the treatment under study has anticancer activity or otherwise improves the well-being of cancer patients.
d Chemotherapy, radiation therapy, hormonal therapy, or cytokine therapy given/allowed at the same time as vaccine therapy.
e For information about levels of evidence analysis and an explanation of the level of evidence scores, see Levels of Evidence for Human Studies of Cancer Complementary and Alternative Medicine.
f Only 48 patients were treated with NDV-infected tumor cell vaccines; the remaining patients were treated with another type of vaccine.
g The patients were divided into groups that received a high-quality vaccine or a low-quality vaccine; the low-quality vaccine groups served as the controls; 32, 13, and 18 patients with early breast cancer, metastatic breast cancer, and metastatic ovarian cancer, respectively, received high-quality vaccines; the corresponding low-quality vaccine groups contained 31,14, and 13 patients.
h There were 39 evaluable patients in this study, but findings were reported for only 24 patients.
i Article does not provide enough information.
|Reference Citation(s) ||Type of Study||Type of Cancer||No. of Patients: Enrolled; Treated; Controlb||Strongest Benefit Reportedc||Concurrent Therapyd||Level of Evidence Scoree|
|||Phase II/III (adjuvant setting)||Melanoma||29; 21; 8||No advantage of vaccine for disease free survival or overall survival ||None||1iA|
|||Phase III (adjuvant setting)||Colorectal with liver metastases||51; 25; 26||Planned subgroup analysis, overall and disease free survival advantages in the colon of cancer patients||Protocol therapy was given after complete surgical resection of primary tumor and liver metastases||1iiA|
|||Phase II||Glioblastoma||35; 23; 87 (concurrent controls identified from within same hospital)||Median progression-free survival of vaccinated patients was 40 wk (vs. 26 wk in controls; log-rank test, P = .024), median OS of vaccinated patients was 100 wk (vs. 49 wk in controls; log-rank test, P < .001)||Protocol therapy after surgical debulking of tumor followed by radiation therapy||2A|
|[15,22]||Phase II trial||Metastatic colorectal ||23; 23; Historical controls ||Improved disease-free survival ||No||3iiA |
|||Phase II trial ||Ovarian||82; 24h; None ||Improved disease-free survival||Yes||3iiDi |
|||Phase II trial||Advanced colorectal||57; 48f; Historical controls ||Improved overall survival||No||3iiiA |
|||Retrospective analysis||Early breast ||63; 63; Internal controlsg||Improved overall survival||Yes||3iiiA|
|||Phase II trial ||Metastatic renal cell ||40; 40; Historical controls ||Improved overall survival, 11 patients with complete/partial responses||Yes||3iiiA |
|||Phase II trial ||Various advanced ||43; 31; None||Complete tumor response, 1 patient||Yes ||3iiiDiii |
|||Phase II||Gastrointestinal tumors, stage IV||25; 25; 0||1 Complete response, 5 partial responses, overall response rate = 24%||None described||3iiiDiii|
|||Phase III||Colorectal ||567; 310; 257 ||Higher mean and median survival for vaccination group compared to the resection group alone ||None described||None describedi|