IgA-based immunotherapy development and evaluation using the blood of healthy volunteers

Cancer immunotherapy has established itself as one of the pillars of cancer
treatment. While all clinical-stage antibodies are of IgG isotype, IgA
antibodies hold great promise as therapeutic agents, and several IgA-based
therapeutic approaches are currently being developed. Unlike IgGs, IgAs
effectively recruit neutrophils, the most abundant cytotoxic cells in humans,
mediating efficient killing of antibody-opsonized tumor cells through a unique
process - trogoptosis. IgA are also much better at attracting
monocytes/macrophages for effective cell killing, as has been shown by previous
studies by Matlung (PMID: 31690649), Dechant (PMID: 17709508), Boross (PMID:
23918228) and others.
In this research, we will investigate the functional potential of engineered
IgA antibodies against tumor markers EGFR and EpCAM to induce tumor cell
killing. As immune effector cell population, cells of the myeloid lineage have
to be used, namely: polymorphonuclear cells (PMNs), among which neutrophils
being the most abundant cell population with high tumor killing potential, as
well as peripheral blood mononuclear cells (PBMCs) which were previously shown
to be potent in tumor cell killing via IgA. To achieve required activity in
tumor killing assays, PMNs and PBMCs should be used fresh. Therefore, the
freshly donated blood of healthy volunteers should be used.

The main objective of the study is to assess efficacy of engineered IgA
antibodies (anti-EGFR, anti-EpCAM) in inducing specific tumor cell killing by
myeloid immune effector cells.
The secondary objectives of the study will be:
-To evaluate relative efficiency in tumor cell killing via different formats of
IgA antibodies;
-To investigate if innate immune checkpoint inhibition enhances the activity of
myeloid cells in tumor cell killing via IgA;
-To establish relevant cell culture models of tumor microenvironment with
immune effector cells, for development and investigation of IgA-based
therapies.

In vitro experimental study; collection of blood from healthy donors for use in
in vitro research.

The research procedure is a venapunction and implies only a minor inconvenience
for the subjects. Since this is a basic procedure, the risks for the
participants are negligible. The subjects would be asked to come for a short (5
min) procedure. Subjects can be asked to donate on multiple occasions, but not
more frequently than once per month. The results of the study are expected to
contribute to the development of a novel cancer immunotherapy modality, which
in the future might benefit patients with severe health conditions (cancer).