Barabas Arpad Z, Cole Chad D, Graeff Richard M, Morcol Tulin, Lafreniere Rene
Department of Surgery, University of Calgary, Calgary, AB, Canada.
Department of Neurosurgery, University of Utah, Salt Lake City, UT, USA.
Hum Antibodies. 2016;24(3-4):45-51. doi: 10.3233/HAB-160294.
Objectives were to: 1) induce a lytic IgG antibody (ab) response (via the so called `third vaccination method') against CD38 antigen (ag) residing on the extra-cellular domain of multiple myeloma (MM) cells in recipient rabbits, by combining the CD38 ag with donor-derived anti-CD38 ag lytic IgG ab into an immune complex (IC); and 2) determine whether abs produced would cause complement-mediated lysis (in vitro) of human MM cells containing CD38 ag. The vaccine was created in a two-step process. First, ab (rabbit anti-CD38 ag IgG ab) was raised in donor rabbits by injections of low molecular weight soluble CD38 ag in Freund's complete adjuvant (FCA) and aqueous solution. Second, transfer of pathogenic lytic IgG ab response into recipient rabbits was achieved by injections of ICs composed of CD38 ag and homologous anti-CD38 ag IgG ab. Consequently, recipient rabbits produced the same ab with the same specificity against the target ag as was present in the inoculum, namely agglutinating, precipitating and lytic (as demonstrated in vitro). In an in vitro study, in the presence of complement, donor and recipient rabbits' immune sera caused lysis of CD38 ag associated human MM cells. The most effective lytic ab response causing sera were those from donor rabbits injected with CD38 ag in FCA and those from rabbits injected with ICs, especially when they were administered in adjuvants. These results provided proof of concept that the third vaccination method has good potential as a stand-alone and efficacious method of controlling cancer.
1）通过将CD38抗原（ag）与供体来源的抗CD38抗原裂解性IgG抗体（ab）结合形成免疫复合物（IC），在受体兔中诱导针对多发性骨髓瘤（MM）细胞胞外域上的CD38抗原的裂解性IgG抗体（ab）反应（通过所谓的“第三次疫苗接种方法”）；2）确定所产生的抗体是否会导致含有CD38抗原的人MM细胞发生补体介导的裂解（体外）。该疫苗通过两步过程制备。首先，通过在弗氏完全佐剂（FCA）和水溶液中注射低分子量可溶性CD38抗原，在供体兔中产生抗体（兔抗CD38抗原IgG抗体）。其次，通过注射由CD38抗原和同源抗CD38抗原IgG抗体组成的IC，将致病性裂解性IgG抗体反应转移到受体兔中。因此，受体兔产生了与接种物中存在的针对靶抗原具有相同特异性的相同抗体，即凝集、沉淀和裂解性抗体（如体外所示）。在一项体外研究中，在补体存在的情况下，供体和受体兔的免疫血清导致与CD38抗原相关的人MM细胞裂解。引起血清裂解的最有效抗体反应是来自在FCA中注射CD38抗原的供体兔以及来自注射IC的兔的血清，特别是当它们在佐剂中给药时。这些结果提供了概念证明，即第三次疫苗接种方法作为一种独立且有效的癌症控制方法具有良好的潜力。
