Earlier this month the Spanish Association against Cancer (AECC) announced the results of its most recent Call. Among the awarded recipients three are VHIO researchers: Alena Gros, Principal Investigator of VHIO´s Tumour Immunology and Immunotherapy Group, Isabel Puig, Post-Doctoral Fellow of our Stem Cells & Cancer Group headed by Héctor G. Palmer, and Elena Senís, Post-Doctoral Fellow of VHIO´s Cellular Plasticity and Cancer Group led by María Abad.
More specifically, Alena received funding under the category Seed Ideas – a program supporting new opportunities in cancer research that if successful, will become consolidated research projects, Isabel received her support from the AECC Investigators 2017 funding initiative, and Elena Senís from the AECC Postdoctoral Scientists 2017 funding. All three are appointed as Principal Investigators of their respective projects, with Isabel and Elena under the leadership of Héctor and María, respectively.
Pioneering a novel strategy to better decipher antitumor T-cell response
Alena Gros and her team´s AECC project will seek to develop a new approach aimed at identifying the personalized repertoire of tumor rejection antigens based on the hypothesis that these antigens and/or types of tumor rejection antigens exist and are currently dodging detection by existing methods which are labor intensive, biased towards specific types of antigens, and fall short in consistently identifying the broader landscape of personalized immunogenic tumor rejection antigens.
“This technology could not only become the new standard to identify epitopes that can be used for active immunization strategies but also to reveal T-cell populations for developing more effective T-cell based immunotherapeutics”, explains Alena.
Importantly, this novel approach could also be adopted to generate a fluorochrome labeled reagent to track a diverse population of T-cells with antitumor specificity, without bias towards a certain type of antigen, which would enable the ´policing´of tumor-specific T-cell responses in cancer patients prior and post treatment with immune checkpoint inhibitors. In so doing, this would greatly enhance our current understanding of pre-existing T-cell response against cancer as well the mechanisms of response and resistance to current immunotherapies employed in the clinic.
In short, thanks to the support received from the AECC, this project promises to significantly advance insights into naturally-occurring T-cell response in patients as well as develop novel, more effective and precise strategies to harness this immune response to treat cancer.
Combatting Colorectal Cancer Progression
The second AECC awarded project will aim to develop a novel inhibitor against the progression of colorectal cancer as well as further insights into relapse in patients suffering from this tumor type – currently occurring in 50% of those patients who undergo curative therapy.
Previous research carried out by VHIO´s Stem Cells and Cancer Group led to the identification of a chemotherapy-resistant subpopulation of cancer cells that can reinitiate tumor growth and therefore be responsible for relapse. These cells may be characterized by the presence of an epigenetic enzyme that could in turn constitute the driving factor behind their survival. Further, the product of this enzyme could also serve as biomarker for the prognosis of disease progression.
Research led by Isabel Puig will decipher the molecular and biological role of this epigenetic enzyme towards better understanding its mechanisms of action, as well as developing an inhibitor as a novel target-directed drug for reducing the frequency of relapse in these patients.
“By developing a novel agent, we will ring in a promising and innovative new therapeutic strategy to eliminate these chemoresistant cancer cells and therefore slam the brakes on tumor regrowth”, observes Isabel.
She will also evaluate this epigenetic mark as a potential biomarker to predict disease reoccurrence in other tumor types including breast and lung cancer.
Unmasking molecular mechanisms underlying cellular plasticity in glioblastoma
Glioblastoma multiforme is the most common and aggressive of all brain tumors, associated with a poor prognosis. There is consequently a critical need to identify new therapeutic targets against this difficult-to-treat disease.
This third AECC funded project led by Elena Senís will combine state-of-the-art molecular biology techniques, mouse models, human patient samples and drug screenings in order to advance insights into the molecular mechanisms governing cellular plasticity in glioblastoma. Based on the hypothesis that dedifferentiation-induced cellular plasticity is essential in glioblastoma initiation and maintenance, its specific targeting could lead to the development of more effective therapies against this disease.
“Using reprograming-induced dedifferentiation as our approach, we hope to better understand the relationship between the acquisition of stem cell properties and tumor initiation. We will also strive to characterize the population of cancer cells with stem cell properties and develop novel treatments to specifically stamp them out”, says Elena.
While this project promises an important forward step towards ultimately improving outcomes for patients suffering from glioblastoma, it will also set out to significantly advance the emerging and exciting field of cellular plasticity and cancer.
With their research lines now underway, our three VHIO AECC awardees have a period of four years through which to develop their projects that collectively seek to accelerate cancer science and develop more powerful anti-cancer therapies with a view to moving faster and getting smarter in our efforts aimed at conquering cancer sooner.