NOVEL ADOPTIVE IMMUNOTHERAPY APPROACH THROUGH MiHA TARGETING
The use of immunotherapy to fight cancer has been qualified as "the most significant scientific breakthrough of 2013” according to Science magazine. Adoptive immunotherapy aims at "mobilizing" a patient's own immune defenses against the disease (cancer cells). The most important target antigens present on cancer cells are the minor histocompatibility antigens (MiHAs). MiHAs can induce strong T-cell responses and many of these antigens have a restricted organ and tissue distribution.
We hypothesized that the priming of T-cells with MiHAs expressed only on hematopoietic cells could induce potent and specific anti-leukemic activity. We have shown in preclinical mice models that injection of T-cells primed against a single MiHA can cure leukemia and solid tumors in mice without causing any GVHD or untoward effects.
We have developed a methodology where we sequentially:
Index the MiHAs make-up of a patient;
Select highly immunogenic MiHAs expressed on the patient neoplastic cells;
Prime and culture T-cells specific to the selected MiHA.
This lays the foundation of a personalized anti-cancer treatment based on our proprietary geno-proteomic approach that hinges on a combination of next generation sequencing and high-throughput mass spectrometry (MS) peptide identification.
Within the last 2 years, we have identified close to 100 new MiHAs.
Currently, we are in the process of:
expanding the representation of MiHAs in order to enable MiHA-targeted therapy of almost 100% of patients with HCs;
assessing which of our MiHAs are the best candidates for leukemia immunotherapy (based on their immunogenicity and expression on HC cells) and;
filing a CTA application with Health Canada to assess the anti-HC activity of MiHA-targeted T-cells in patients. Planned "first-in-man" study will be initiated in Q3 2016.
Adoption of MiHA-targeted immunotherapy would allow for a safer, better targeted and more effective treatment of patients with otherwise fatal HCs without increasing the global cost of HC treatment.
The use of next-generation MiHA-targeted allogeneic hematopoietic cell transfer therapies will reap the following benefits:
Improve the anti-tumor response hence, increase the success of AHCT;
Decrease the incidence of GVHD and associated costs related to GVHD long term treatments;
Offer an alternative immunotherapy solution suitable for all patients afflicted with HC and ideal for patients for whom suitable donors or weak alloresponders cannot be found.
Combining the GVHD genetic prediction test together with a strengthened MiHA-targeted immunotherapy will significantly increase the proportion of patients who can benefit from immunotherapy (standard AHCT or MiHA-targeted). This will have a significant impact on patient survival and healthcare costs. Over time, up to 50% of patients with refractory HC will be offered access to this most powerful tool which is adoptive immunotherapy.