Current treatments lack selectivity towards cancer cells, which induces insufficient anticancer activity and produces severe adverse effects that limit their dosage. We are developing self-assembling protein-based nanoparticles for the treatment of hematological and solid cancers that are highly selective in targeting receptors overexpressed in cancer stem cells. They display a wide therapeutic window by avoiding renal clearance while internalizing into and selectively eliminating cancer target cells and enhancing the uptake of the payload drug into cancer tissues, with negligible uptake or toxicity in normal tissues.
We have achieved high antitumor and antimetastatic effects using apoptotic, genotoxic or microtubule inhibitor drugs as payloads, and we are now testing novel payloads that use non-apoptotic cell death mechanisms.
We generate novel protein-based nanomedicines with a high therapeutic window that tackle unmet treatment needs in acute myeloid leukaemia (AML), diffuse large B-cell lymphoma (DLBCL) and colorectal cancer (CRC) using preclinical models and clinical translation, through:
The development of animal cancer models that are resistant to current therapy or disseminated for the study of the molecular mechanisms of cancer stem cell involvement in these processes, especially in cancer cells that overexpress the chemokine receptor CXCR4.
The development of drug nanoconjugates or protein-only nanoparticles for intravenous injection that use receptor-mediated targeted delivery of cytotoxic agents to cancer stem cells and incorporate novel drugs or polypeptide domains that exploit the higher capacity for apoptotic induction, or the triggering of cell death mechanisms as an alternative to apoptosis.
The development of artificial amyloid bodies for subcutaneous injection with capacity for the sustained release of therapeutic protein nanoparticles in the bloodstream that reach cancer tissues.
Our aim is to develop nanomedicines that can effectively render cancers that have disseminated or relapsed sensitive to therapy by acquiring resistance to current therapy. In doing so, we expect to increase the cure and complete response rates, thereby leading to longer survival times.
An additional goal is to ensure that the repeated administration of these novel nanomedicines induces potent anticancer activity, while maintaining low or absent toxicity in normal tissues, associated with a lack of, or tolerable, side effects.
Finally, we also aim to develop a formulation of amyloid structured inclusion bodies whose capacity for the sustained release of therapeutic nanoparticles into the blood could be subcutaneously administered once a month. Their development will circumvent the need to administer the nanoparticles twice a week by intravenous injection, thus allowing patients to stay at home during treatment and avoid hospitalization.
Ninety percent of cancer patients die of metastases that do not respond to current treatments. Therefore, patients who develop metastases are considered incurable. Through our research, we aim to answer the following questions:
Is the selective elimination of cancer stem cells a relevant clinical target to improve therapy in different cancer types with acquired resistance and disseminated disease?
Will protein-based targeted nanoparticles that incorporate non-apoptotic and immunogenic cell death polypeptides increase cure, response and survival rates while reducing side effects once tested in patients?
What are the underlying mechanisms that dictate the highly selective accumulation of protein nanoparticles targeting the CXCR4 receptor we observe in cancer tissues?