Authors
Chernyavska, M., Hartmann, K. P., Jansen, M., Baumann, N., Kolibius, J., Bruecher, D., Kristoforus, T., Peters, R. H. W., Huijs, L., Laarveld, D., Weiss, F., Burger, R., Lustig, M., Gimenez de Assis, N., Schmid, M., Leusen, J. H. W., Valerius, T., Plueckthun, A., Verdurmen, W. P. R.
Abstract
Despite advances in IgG-based cancer immunotherapy, challenges remain in effectively engaging innate immune responses against solid tumors. Here, IgA antibodies hold promise due to their ability to activate neutrophils and macrophages. We present a novel retargeted adenovirus-mediated approach that transforms cancer cells into biofactories for localized production of monomeric or dimeric IgA antibodies and a CD47 blocker to potentiate the effect of IgA antibodies. With our approach tumor cells effectively produced IgA antibodies against tumor antigens such as EGFR or EpCAM and a soluble SIRP-alpha-Fc fusion protein, which blocks the CD47-SIRP-alpha; axis. In a perfused tumor-on-a-chip model, locally produced IgA triggered neutrophil- and macrophage-mediated tumor cell killing, further potentiated by SIRP-alpha-Fc co-production. In FcalphaRI-transgenic, tumor-bearing mice, intratumoral adenoviral injection induced strong local IgA and SIRP-alpha-Fc expression, immune cell infiltration, and more than 50% tumor volume reduction after a single treatment. We found that dimeric IgA exerts stronger effects than monomeric IgA, which is of particular interest since dimeric IgA necessitates a local production approach. Together, these results demonstrate that adenovirus-mediated, tumor-restricted delivery of IgA antibodies and CD47 blockade effectively engages innate immune mechanisms, providing a promising new avenue to enhance cancer immunotherapy.
Preprint server:
bioRxiv
The authors list and abstract were imported from bioRxiv on 08 Nov 2025.
Advertisement
Stats
- Recommendations n/a n/a positive of 0 vote(s)
- Views 31
- Comments 0