Info

a QS21 = saponin extract from the bark of the South American soap bark tree Quillaja saponaria monila. b (n) number of patients. c CR = complete response. d SD = stable disease.

e BCG = attenuated strain of Mycobacterium bovis. f KLH = keyhole limpet hemocyanin.

a QS21 = saponin extract from the bark of the South American soap bark tree Quillaja saponaria monila. b (n) number of patients. c CR = complete response. d SD = stable disease.

e BCG = attenuated strain of Mycobacterium bovis. f KLH = keyhole limpet hemocyanin.

caused by the malignant disease. This possibility is supported by the higher immune response elicited in healthy animals than in patients with melanoma by anti-id mAb which mimic distinct determinants of the HMW-MAA. Specifically, the anti-id mAb MK2-23 has induced anti-HMW-MAA antibodies in all the immunized rabbits [79], but in about 60% of patients with melanoma [38, 70], Furthermore, the anti-id mAb Mel-2 has induced anti-HMW-MAA antibodies in cynomolgus monkeys [80], but not in patients with melanoma [81]. However, one cannot exclude that these differences reflect the extent of mimicry by anti-id mAb of determinants on human TAA and on the counterpart expressed in the animals used for the immunization experiments. This possibility should be taken into account especially since no significant difference in the level of antibodies to constant regions of the immunizing mouse anti-id mAb has been found between patients who have developed TAA binding anti-anti-id antibodies and those who have not. An alternative, but not exclusive mechanism to explain the difference in the anti-anti-id response of the immunized patients is represented by the inability of some of them to recognize the idiotope which mimics the TAA

determinant. Whether the patients' immune response to the internal image of the TAA determinant is HLA linked remains to be determined. This possibility is suggested, at least in some TAA systems, by the difference in the ability of H-2 congenic mouse strains to develop HMW-MAA binding antibodies (unpublished results) following immunizations with anti-id mAb MK2-23. The latter bears the internal image of the antigenic determinant defined by anti-HMW-MAA mAb 763.74 [38, 79, 82],

(iii) The level of TAA binding anti-anti-id antibodies elicited in patients has been found to be low in all the clinical trials. In the GD3 ganglioside system, anti-anti-id antibodies have been found to react with synthetic GD3 ganglioside, but not with GD3 ganglioside expressed on tumor cells [77]. This finding has been suggested to reflect the low avidity of GD3 ganglioside binding anti-anti-id antibodies for membrane bound GD3 ganglioside. The low level and the low association constant of TAA binding antibodies elicited by anti-id antibodies are not likely to reflect malfunction of patients' immune system because of malignant disease induced immune suppression, since similar characteristics have been found in the anti-

Table 7. Sequence of the peptides derived from anti-id mAb Mel-1 with HLA-A2 antigen binding motifs

Sequence

Position

Binding scorea

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