Chattopadhyay P, Kaveri S V, Byars N, Starkey J, Ferrone S, Raychaudhuri S
IDEC Pharmaceuticals Corp., La Jolla, California 92037.
Cancer Res. 1991 Nov 15;51(22):6045-51.
The mouse anti-idiotype (anti-id) monoclonal antibody (mAb) IMel-1 recognizes an idiotope in the antigen combining site of the immunizing anti-human high molecular weight melanoma-associated antigen (HMW-MAA) mAb 225.28. The mAb IMel-1 is able to induce an immune response against self cross-reacting HMW-MAA in rabbits that express HMW-MAA in normal tissues. Most of the rabbit anti-anti-id antibodies recognize a spatially distant determinant(s) from that defined by anti-HMW-MAA mAb 225.28. The immunogenicity of mAb IMel-1 is enhanced by its administration with the muramyl dipeptide-derived adjuvant. Anti-HMW-MAA antibodies were not detected in sera from rabbits immunized with HMW-MAA bearing cultured human melanoma cells. The differential immunogenicity of mAb IMel-1 and cell membrane bound HMW-MAA may account for the ability of anti-id mAb to induce anti-HMW-MAA immunity in patients who have not mounted such a response to HMW-MAA present in their lesions. Rabbit anti-HMW-MAA antibodies induced by anti-id mAb IMel-1 inhibited interactions of melanoma cells with elements of extracellular matrix. This may represent an additional mechanism by which anti-HMW-MAA immunity may affect the biology of melanoma cells in patients with melanoma immunized with anti-id mAb IMel-1.
小鼠抗独特型（抗Id）单克隆抗体（mAb）IMel-1识别免疫用抗人高分子量黑色素瘤相关抗原（HMW-MAA）单克隆抗体225.28抗原结合位点中的一个独特型表位。单克隆抗体IMel-1能够在正常组织中表达HMW-MAA的兔体内诱导针对自身交叉反应性HMW-MAA的免疫应答。大多数兔抗抗独特型抗体识别的决定簇与抗HMW-MAA单克隆抗体225.28所界定的决定簇在空间上相距较远。单克隆抗体IMel-1与胞壁酰二肽衍生佐剂一起给药可增强其免疫原性。在用携带HMW-MAA的培养人黑色素瘤细胞免疫的兔血清中未检测到抗HMW-MAA抗体。单克隆抗体IMel-1与细胞膜结合的HMW-MAA的免疫原性差异可能解释了抗独特型单克隆抗体在对其病变中存在的HMW-MAA未产生此类应答的患者中诱导抗HMW-MAA免疫的能力。抗独特型单克隆抗体IMel-1诱导的兔抗HMW-MAA抗体抑制了黑色素瘤细胞与细胞外基质成分的相互作用。这可能代表了抗HMW-MAA免疫可能影响用抗独特型单克隆抗体IMel-1免疫的黑色素瘤患者中黑色素瘤细胞生物学的另一种机制。
