1994 Fiscal Year Final Research Report Summary
ANALYSIS OF MELANOMA IDIOTYPE NETWORK AND IT'S CLINICAL APPLICATION
| Project/Area Number |
05670735
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Dermatology
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| Research Institution | KUMAMOTO UNIVERSITY |
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Principal Investigator |
KAGESHITA Toshiro KUMAMOTO UNIVERSITY,DEPARTMENT OFDERMATOLOGY,ASSISTANT PROFESSOR., 医学部・付属病院, 講師 (20152605)
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| Project Period (FY) |
1993 – 1994
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| Keywords | MELANOMA / IDIOTYPE NETWORK / ANTI-IDIOTYPIC MONOCLONAL ANTIBODY |
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| Research Abstract |
(1) Analysis of idiotype network in melanoma
The mouse anti-id mAb MK2-23 bears the internal image of the antigenic determinant defined by anti-HMW-MAA mAb 763.74.8HMW-MAA binding anti-anti-id Mabs elicited with mAb MK2-23 were characterized in their reactivity with a large panel of surgically removed benign and malignant melanocytic tumors. The 8 anti-anti-id mAbs displayd subtle differences in their immunoperoxidase staining of both benign and malignant tumors. The diversity in the fine specificity of the 8 anti-anti-id mAbs is likely to reflect the few somatic mutations which occur in the amino-acid sequence of the variable regions of their heavy and light chains in the course of the immune response to mAb MK2-23. The reactivity patterns of the 8 anti-anti-id mAbs with the tissue substrates are similar, although not superimposable upon that of the anti-HMW-MAA mAb 763.74 elicited with melanoma cells. This difference may reflect the imperfect mimicry by anti-id mAb MK2-23 of the antigenic determinant defined by anti-HMW-MAA mAb 763.74.
Moreover the amino-acid sequences of 8 anti-anti-id mAbs were compared with that of anti-HMW-MAA mAb 763.74.80-95% and 85-100% homology were seen in the amino-acid sequence of the variable regions of their heavy and light chains, respectively. The highest homology was found in CDR1 and lowest in CDR3.
(2) Induction of delayd type hypersensitivity by anti-id mAb.
Cell mediated DTH reaction to cultured human melanoma cells Colo38 in BALB/c mice was done by immunized with anti-id mAb MK2-23 and unrelated isotype-matched anti-id mAb TK6-74. Irradiated Colo 38 cells injected into the right hind pad of the previously immunized mice and irradiated cultured human B lymphoid cells LG-2 were injected into the left side as control. Only MK2-23 could induce DTH reaction to HMW-MAA bearing human melanoma cells Colo38.
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