Oncogenesis and Antitumour Drugs

We are developing protein-based targeted nanoparticles that inhibit translation and nanoconjugates to selectively ablate cancer stem cells or cancer-associated fibroblasts and their combination with inhibitors of immune checkpoints to improve the current treatment of solid tumors and hematological neoplasms. We also generate immunosuppressed and immunocompetent cancer mouse models, either subcutaneous or orthotopic, to preclinically evaluate the anticancer effect of these nanomedicines and their associated toxicities with the goal of reaching clinical translation and industrial transference.

Main Lines of Research

• Development of targeted nanoparticles that incorporate bacterial toxins to generate local tumor pyroptosis and noncanonical transcripts and translons to recruit and activate T cells in tumor and metastatic tissues. Moreover, the combination of the nanoparticles with immune checkpoint inhibitors and T cell receptor agonists that reverse immune exhaustion, with the goal that this immunotherapy induces a response in microsatellite stable solid cancers (Mangues Bafalluy, Ramon).
• To develop a humanized auristatin-based nanoconjugate targeting leukemic stem cells for the treatment of acute myeloid leukemia. Within this line of research, the activity of this nanoconjugate is being evaluated in cell-derived xenograft (CDX), patient-derived xenograft (PDX), and humanized murine models. We are also investigating its ability to activate the immune system and its potential synergy with other precision therapies. (Casanova Rigat, Isolda).
• Rational engineering of multivalent, receptor-targeted protein nanoparticles as precision nanodrugs for cancer therapy. This line seeks to offer innovative therapeutic solutions based on the rational design, production, and validation of self-assembling protein nanocarriers that allow the selective delivery of therapeutic protein domains and/or conjugated payloads to tumor cells, with the goal of maximizing on-target efficacy while minimizing systemic toxicity. (Unzueta Elorza, Ugutz).
• Development and preclinical validation of tumor-microenvironment-targeted nanoparticles. This research line focuses on targeting cancer-associated fibroblasts within solid tumors to reprogram the tumor microenvironment, reduce cancer cell aggressiveness, prevent metastatic dissemination, and sensitize tumors to standard-of-care therapies. (Alba-Castellon, Lorena).

Scientific Challenges

• To develop nanomedicines based on preclinical protocols able to induce unannotated transcripts to achieve effective immunogenic cell death in solid tumors, which are currently resistant to immunotherapy.
• To develop new protein nanoconjugates for targeted delivery of antitumor drugs with innovative mechanisms of action for the treatment of tumors resistant to common drugs.
• To develop efficient protein nanovehicles for the targeted delivery of therapeutic nucleic acids to tumor cells in vivo as an alternative to viral vectors.
• To develop protein nanopharmaceuticals for the activation of the immune system against cancer as a more effective nano-immuno-oncology approach than current treatments.
• To develop targeted nanotherapy to reprogram the tumor microenvironment to enhance their antitumor role.

Contact

Ramon Mangues
rmangues@santpau.cat