AIMM’S PROPRIETARY AIMSelect™ AND AIMProve™ TECHNOLOGY PLATFORMS TO GENERATE HIGH AFFINITY HUMAN MONOCLONAL ANTIBODIES
AIMM Therapeutics has developed a highly versatile proprietary platform that can be used to immortalize the entire B cell repertoire from whole blood or germinal centers. The platform also includes the ability to affinity mature the selected B cell clones to produce high quality fully human monoclonal antibodies with tailored properties.
Immortalization of the human B-cells in our AIMSelect™ platform is achieved by the introduction of the genes Bcl-6 and Bcl-xL which prevent growth arrest and apoptosis of the B cells. The very stable, rapidly proliferating immortalized B cells express surface immunoglobulin and secrete antibody. These features allow the selection of the desired monoclonal antibody either by binding of labeled antigen to the surface immunoglobulin or by specific neutralizing activities of the secreted antibodies. If desired, the antibodies can be further affinity matured utilizing a proprietary ex-vivo process (AIMProve™) obviating the need of time-consuming and labor-intensive molecular engineering. The B cell lines generated by AIMSelect™ express activation induced deaminase (AID), the enzyme that is responsible for mutations in immunoglobulin genes leading to antibodies with higher affinity by applying fast screening techniques AIMM is able to obtain sub-clones of antigen-specific B cells producing monoclonal antibodies with exceptional affinities. AIMM Therapeutics also has a novel site-specific protein coupling technology in place, AIMLink™, which allows efficient production of bispecific monoclonal antibodies with a defined composition, which maintain the affinities of each of the individual partners. The versatility of AIMSelect™ platform allows for the production of therapeutic antibodies with high affinity and superior physico-chemical properties in time frames from 3-6 months.
AIMM Therapeutics has successfully exploited the AIMSelect™ platform to immortalize human antibody-producing B cells covering the complete antibody repertoire of the donor. The immortalized B cells are exceptionally stable, allowing rapid isolation of cloned antigen specific B-cell lines producing superior quality antibodies. Antibodies to ‘self or tumor associated antigens ’ with high therapeutic potential are obtained from B cells of patients suffering from cancer or autoimmune- and inflammatory diseases. Clinically relevant antibodies are also obtained from individuals who successfully combated disease-causing microbes or viruses. The validation of this approach is evidenced by three licensing deals for AIMM antibodies that are currently in, or completing late stage IND enabling studies.
AIMM Therapeutics also utilizes a mouse with a human immune system to obtain antibodies against any antigen of choice. Mice with a crippled immune system of their own develop a functional human immune system after injection with human blood stem cells. Using the AIMSelect™ platform we can isolate antigen-specific antibody-producing B cells from immunized mice. This technology has broad applicability to contemporary antibody development where animals that incorporate human immunoglobulin transgenes are used to generate monoclonal antibodies. Using AIMM Select, this entire B cell repertoire can now be selected and cloned, and further affinity matured if desired resulting in far more efficient human antibody production process.