INVITRO AND CLINICAL CHARACTERIZATION OF A NEWCASTLE-DISEASE VIRUS-MODIFIED AUTOLOGOUS TUMOR-CELL VACCINE FOR TREATMENT OF COLORECTAL-CANCER PATIENTS

A virus-modified autologous tumour cell vaccine prepared from human colorectal cancer cells is described. After dissociation an average of 5 x 10(7) cells/g tissue were obtained from primary tumours and 9 x 10(7)/g tissue from metastases with an average viability of 72% and 51%, respectively. Following irradiation (200 Gy), inactivation of the proliferative activity of the cells was demonstrated by their degeneration in tissue culture and the absence of incorporation of H-3-labelled thymidine. One third of the cells were still metabolically active, as shown by the incorporation of H-3-uridine and a mixture of H-3-aminoacids. The dissociated cells expressed MHC class I and II antigens in a qualitatively similar way to tissue sections. Epithelium-specific antigens (detected by MAb HEA125) were expressed on an average of more than 75% cells of the suspension, while leucocyte-specific antigens (detected by MAb CD53) were expressed on an average of less than 25% cells. The vaccine was prepared by admixing the nonlytic strain Ulster of Newcastle disease virus (NDV) with the tumour cell suspension. The NDV adsorption at tumour cells was shown by electron microscopy. Clinically, the treatment with the vaccine was associated with an increased sensibilisation against autologous tumour cells, measured by DTH skin reactivity. First results in 23 patients with colorectal liver metastases who underwent "curative" liver resection followed by vaccination show a clear correlation between the induced increase of DTH skin reaction against autologous tumour cells and the recurrence-free interval. No correlation was found for DTH reaction caused by standard antigens (Merieux test), NDV alone or autologous normal liver tissue. The results demonstrate the possibility of preparing immunogenic virus-modified autologous tumour cell vaccine from colorectal cancer tissue, which could be used for cancer therapy.