Recombinant polyclonal antibodies for cancer therapy

Abstract

Although monoclonal antibodies are increasingly used for cancer therapy, remissions are only temporary due to emergence of tumor cell escape variants that are no longer affected by the antibody. The emergence of escape variants could be minimized by multi-targeting of tumor cells with polyclonal antibodies, which would also be more efficient than monoclonal antibodies at mediating effector functions for target destruction. A technology for generating recombinant polyclonal antibodies for cancer therapy has been developed based on the construction and selection of tumor-reactive Fab phage display libraries. The selected Fabs are mass-converted to full-length polyclonal antibody libraries (PCALs) of any isotype and any species. Prototypic PCALs generated against human colorectal cancer cell lines showed that libraries of diverse recombinant antibodies, enriched for reactivity to the cancer cells compared to normal human cells, can be obtained. The success of recombinant polyclonal antibodies as cancer therapeutics will depend on the ability to generate, characterize, and mass-produce PCALs with high ratios of cancer-to-normal reactivities that crossreact with many cancers of the same type.

Generation and characterization of hybridoma antibodies for immunotherapy of tularemia

“…LVS infection although the effect was not statistically significant. Because Ab12 is of the IgG3 isotype, like the least effective LPS-binding Ab2, we expect that recombinant DNA conversion of Ab12 into an IgG2a version [53,54] will increase its efficacy. Of the other anti-LVS IgG hybridoma antibodies, the DnaK-specific Ab13 and Ab31 (both IgG1) were ineffective against LVS even though the LPS-binding IgG1 Ab9 showed some efficacy.…”

“…Similarly, the IgG2a Ab10, specific for the 50S ribosomal protein L7/L12 showed no protection, consistent with the expected cytoplasmic location of the target antigen, even though L7/L12 was previously described as potentially surface-exposed and as an immunoreactive protein in sera from mice immunized with LVS or F. tularensis novicida [34], and in sera from tularemia patients [38,39]. The induction of antibodies with no protective function during infection underscores the advantage of the hybridoma and recombinant DNA technologies over the use of serum antibodies for immunotherapy, as the former allow for selection of antibodies of only the desired specificities, in addition to their conversion into antibodies with C regions of desired isotypes and species [53,54].…”

“…A recombinant polyclonal antibody would target multiple bacterial epitopes, which would enhance effector functions and decrease the likelihood of emergence of antigen-escape variants, as we previously suggested [54,55]. Such recombinant polyclonal antibodies are already being produced for clinical therapeutic use [56], and the first such product has recently entered Phase I clinical trials (for treatment of hemolytic disease of the newborn and/or idiopathic thrombocytopenic purpura) (http://www.symphogen.com).…”

The potential of porous silicon particles for multi-epitopic vaccine development

“…Therefore, major efforts are needed to improve the efficacy of immunotherapies. In this sense, the use of monoclonal antibodies against different TAAs (Sharon et al 2005) has been proposed as well as the use of antibody-mimicking agents targeting several epitopes (Nahta et al, 2006;Pal and Pegram, 2007).…”

Identification of Clinically Significant Tumor Antigens by Selecting Phage Antibody Library on Tumor Cells in Situ Using Laser Capture Microdissection

“…In addition, antibodies targeting internalizing tumor epitopes could be exploited to achieve efficient and specific intracellular delivery of chemotherapeutic drugs or other tumor-modulating agents (1, 10 -12). Phage antibody display has been widely used to develop cancer-specific antibodies (1,(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23). A combinatorial phage antibody library serves as a source of random shape repertoire that can be used to probe neoplastic variations on the surface of cancer cells (1, 24 -26).…”