A unique foundation for discovery

AIMM was founded based on proprietary and groundbreaking B-cell immortalization technologies.

Using our method of retroviral transduction, the total B cell repertoire from cancer survivors can be interrogated to identify unique and specific antibodies (AIMSelect). Immortalized B-cell clones demonstrate expression of activation-induced cytidine deaminase (AID), which through our AIMProve platform, we are able to isolate affinity variants of the originally identified antibody and cloned antibody. Using this approach we have been able to improve the affinity of some of our lead candidates more than 100-fold.

AIMSelect

The power and uniqueness of AIMM’s approach rests on our ability to immortalize the human immune system’s memory B cell repertoire by transforming these cells into long living plasmablasts. This is achieved via our proprietary platform in which the genes of the anti-apoptotic Bcl-xL and the transcriptional repressor Bcl6 molecules are retrovirally transduced into the memory B cells.

The transduced B-cell clones express the B cell receptor on their surface and secrete immunoglobulins into the culture supernatant. These attributes enable AIMM to directly select B cells from the entire B cell collection based on either antigen specificity or biological function. Transduction efficiencies approaching 90% are frequently observed, allowing the interrogation of the entire human B cell repertoire. This, combined with functional testing or affinity-based selection, enables the rapid selection of cancer-specific B-cells from the entire B cell population.

AIMM has successfully deployed its AIMSelect platform to immortalize the complete B cell antibody repertoire, including immature, switched and hypermutated B cells. Most notably, our platform was clinically validated by the identification of D25, an anti-RSV antibody that is currently being advanced in Phase 3 clinical trials by Medimmune/AstraZeneca as Nirsevimab (MEDI-8897). Additionally, our platform has been validated using B-cells from multiple species. The scientific rigor of the platform served as the basis for an exclusive license by Merck/Millipore to use our platform to isolate reagents and diagnostics (Zoomabs).

AIMProve

Following immortalization of B-cell clones using AIMSelect, the antibodies produced by such clones can be further matured to improve their affinity for the target using the ex-vivo AIMProve platform. AIMProve is based on the notion that immortalized B cell clones express the enzyme activation-induced cytidine deaminase (AID). AID is the enzyme that drives somatic hypermutation of a B cell’s immunoglobulin genes. Using our proprietary selection strategy, it is possible to progressively enhance or reduce the affinity of antibodies produced by the B cell in an unbiased way. Utilizing AIMProve we have been able to rapidly generate sub- clones of antigen-specific B cells that produce antibodies with exceptional (more than 100-fold increase in) affinities for an antigen.

Publications