Antibody Discovery and Therapeutic Approval

About 50%

www.antibodysociety.org/antibody-therapeutics-product-data/

Not specified in the text, but can be calculated from the data

From Antibody Discovery till Therapeutic Approval

Rene Hoet

Monospecific antibodies bind to a single target, while bispecific antibodies bind to two targets.

Bispecific antibodies can achieve greater efficacy on a single patho-mechanism and address multiple patho-mechanisms simultaneously.

Tunable stoichiometry allows for the ability to adjust the ratio of binding to the two targets (A and B), such as 1A:1B, 2A:1B, or 2A:2B.

CD20 x CD3 bispecific T cell engagers.

Bispecific antibodies can enable first-in-class therapies by activating two co-receptors/co-factors, enhancing receptor inhibition, or increasing therapeutic window through cell-specific targeting.

Bispecific antibodies can increase therapeutic window through cell-specific targeting, allowing for more precise and effective treatment.

To select antibodies for developability

10^9 CFU

10^27 CFU

Mimicking FVII

Activating γδT cells

Improved developability and high affinity/potency

To explore 1027 diversity and select heavy chain and light chain scaffolds that are most frequently used in humans.

To mimic human diversity in the heavy and light chains.

By incorporating microfluidics technologies for soluble functional screening and 'shuffling' modules in the final antibody format.

To reduce biophysical liabilities and improve the developability of the antibodies.

It enables the generation of highly developable antibodies with a total diversity of 1027 individual modules.

To obtain CDR3-H3 and CDR3-L3 diversity from human donors.

Current limitations of immunotherapy include the ability of tumors to escape immune surveillance by downregulating the immune system. These limitations can be addressed through new approaches to induce immune response, such as targeting 'cold tumors' and combining immunotherapies with other treatments.

gd T-cells have a dual effect of direct tumor lysis and immune response modulation. They also have high frequency and tumor-infiltrating capabilities in many cancers, are not restricted by MHC alleles, and have no correlation with αβ TILs, making them a promising target for immunotherapy.

The current focus of immunotherapy research is on new combinations of immunotherapies, including targeting CTLA-4 and PD-1(PD-L1) for additional cancer indications. The challenge is that only a subset of patients respond to these treatments, and new approaches are needed to induce immune response.

Approved antibodies as inhibitors of immune checkpoint regulators, such as aCTLA-4, aPD1, and aPDL1, have been shown to be effective in treating certain cancers, but there is still a need for new approaches to induce immune response.

gd T-cells differ from αβ T cells in that they have no correlation between αβ TILs and TCR Vγ9Vδ2+ γδ TILs, making them a distinct population of immune cells. This difference has implications for immunotherapy, as gd T-cells may be a promising target for combination therapies.

The prognostic impact of genes and infiltrating immune cells across cancers suggests that the presence of certain immune cells is correlated with favorable clinical outcomes. This has implications for immunotherapy, as targeting these immune cells may improve patient outcomes.