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

Methodology

Generation of stable monoclonal antibody-producing B cell receptor-positive human memory B cells by genetic programming.

Kwakkenbos MJ, Diehl SA, Yasuda E, Bakker AQ, van Geelen CMM, Lukens MV, van Bleek GM, et al.
Nat Med 2010; 16: 123–128

Genetic manipulation of B cells for the isolation of rare therapeutic antibodies from the human repertoire.

Kwakkenbos MJ, Bakker AQ, van Helden PM, Wagner K, Yasuda E, Spits H, Beaumont T.
Methods 2014; 65: 38–43

Stable long-term cultures of self-renewing B cells and their applications.

Kwakkenbos MJ, van Helden PM, Beaumont T, Spits H.
Immunol Rev 2016; 270: 65–77
AT1636

A colon cancer survivor-derived antibody recognizes a previously unidentified truncated, O-mannosylated 70kDa variant of E-cadherin

Kedde M, Beaumont T, Merat SJ, Kwakkenbos M, Bartels L, van de Berg D, Claassen YB, Moiset G, Wagner K, Bakker AQ, Maijoor K, Bohne M, Bru C, Kattler V, van Eenennaam H, Roos VH, Kallenberg F, Medema JP, Hensbergen PJ, van Helden P, Dekker E, Spits H.
AACR 2020 virtual II meeting
AT1413

Patient-derived antibody recognizes a unique CD43 epitope expressed on all AML and has antileukemia activity in mice.

Gillissen MA, Kedde M, de Jong G, Moiset G, Yasuda E, Levie SE, Bakker AQ, et al.
Blood 2018; 131: 131–143

A Chemo-enzymatically Linked Bispecific Antibody Retargets T Cells to a Sialylated Epitope on CD43 in Acute Myeloid Leukemia.

Bartels L, de Jong G, Gillissen MA, Yasuda E, Kattler V, Bru C, Fatmawati C, et al.
Cancer Res 2019; 79: 3372–3382

T-cell engager bispecific formats of an AML patient-derived antibody targeting a unique sialylated CD43 epitope induce kill of melanoma cells in vitro and in vivo

de Jong G, Bartels L, Kedde M, Verdegaal E , Gillissen MA, Levie SE, Cercel MG, van Hal-van Veen SE, Fatmawati C, van de Berg D, Yasuda E, Claassen Y, Bakker AQ, van der Burg SH, Schotte R, Villaudy J, Wagner K, Spits H, Hazenberg MD, van Helden PM.
AACR 2020 virtual II meeting
AT1412

A patient-derived anti-CD9 antibody induces tumor rejection and synergistically enhances anti-PD1 activity

Schotte S, Villaudy J, Kedde M, Pos M, Wagner K, Neviani V, Go D, Fatmawati C, Verdegaal E, van Hal S, Bru C, Claassen Y, van Eenennaam H, van Helden P, van der Burg S, Gros P, Spits H.
AACR 2020 virtual II meeting

AT1412, a Patient-Derived Antibody in Development for the Treatment of CD9 positive B-Acute Lymphoblastic Leukemia

de Jong, G, Levie, SE, Schotte, R, Pos, W, Go, D, Yasuda, E, Cercel, MG van Hal-van Veen, SE, Frankin, E, Szabó, A, Kedde, M, Verdegaal, E, Villaudy, J, van der Burg, S, van Helden, PM, van Eenennaam, H, Spits, H, Rijneveld, AW, Hazenberg MD.
AACR 2020 virtual II meeting
AML specific antibodies

AML-specific cytotoxic antibodies in patients with durable graft-versus- leukemia responses.

Gillissen MA, Kedde M, de Jong G, Moiset G, Yasuda E, Levie SE, Bakker AQ, et al.
Blood 2018; 131: 131–143