2015 MPN Challenge Grant

The 2015 MPN Challenge is a grant program supported jointly by the MPN Research Foundation and the Leukemia & Lymphoma Society. This grant program represents an important partnership between MPNRF and LLS, who share a mission to advance the scientific understanding of MPNs and bring new treatments and the hope for a cure to patients with these rare diseases. Click here to see the winners of this grant.

We hear from patients with MF, PV and ET and they have concerns about symptoms, treatment options, and quality of life, but their most pressing question is – will my disease progress, will I get MF, will I convert to AML?

The emergence of new treatments for MPN patients is encouraging, but until there is proof that these emerging treatments actually change the course of these diseases, these fears will remain. The MPNRF and LLS want to change this with a focus on new approaches towards MPN research that may change the trajectory of these diseases. We hope that independent researchers will join us in an attempt to achieve that goal.

The 2015 MPN Challenge

The goal of the 2015 MPN Challenge is to ensure that MPNs are evaluated as candidates for new transformative technologies currently being investigated for other cancers. We want to attract investigators in other fields whose research may apply to MPN research.

Why this Approach is Appropriate Now

Based on the response to the MPN Challenge in recent years, MPNRF and LLS are encouraged that ‘paradigm-shifting’ strategies identified in other areas of cancer and basic biology research can be useful in the search for MPN treatments. In 2014 alone, there have been significant advances in immunotherapy, gene editing and other technologies as applied to solid tumor and other cancers. If applied to MPNs, these new strategies, in combination with currently emerging treatments, could truly change the course of the MPNs.

Focus Areas for 2015 MPN Challenge Grants

To guide us, in November 2014, the MPN Research Foundation convened a group of scientists from both academia and industry to discuss the unmet needs in MPN research. This diverse group of current MPN Challenge grantees, academic scientists and representatives of companies currently involved in MPN treatment development held a lively discussion that resulted in the following list of focus areas for the 2015 MPN Challenge:

1. Targeting the Malignant JAK2 Clone

Research in this area will provide a better understanding of the importance of the JAK2 allele burden and mechanisms for reducing it in MPN patients, including the following areas:

• studies aimed at determining the significance of JAK2 allele burden as a diagnostic tool.
• research aimed at identifying and testing JAK inhibitors that inhibit the mutant and not the wild-type allele.
• preclinical testing of new agents that demonstrate potential to reduce the JAK2 allele burden.
• basic research and preclinical testing of agents that target the malignant stem cell specifically.

2. Application of Immuno-therapy Approaches to MPNs
This research will investigate the potential for immunotherapy or immune manipulation. Proposals for immune-therapeutic approaches to the broader spectrum of MPNs could include:

• Assessment of the potential role of chimeric antigen receptor therapy (CAR-T) to MPNs.
• Exploration of the role of immune checkpoint regulators in MPNs, e.g., CTLA-4, PD-1, PD-L
• Preclinical testing of antibodies that target the CALR mutated allele.
• Therapy targeted to inflammatory cytokines and/or cytokine receptors and their downstream effectors.
• An understanding of how to combine any of these with evolving therapies for MPN and in particular, since newly approved agents such as pan-JAK inhibitors have potential to impair immune cell activation and function, how or should they be used with immune-modulatory agents.

Proposals that have clear translational potential will be prioritized. The best proposals will include a strong collaboration between current immunotherapy experts and MPN specialists.

3. Gene Editing as Applied to MPNs.
We want to study whether CRISPR or other gene editing technologies can be applied to MPNs. Our primary objective is to make sure that MPNs are on the table as these technologies are developed. The best proposals will include a strong collaboration between current CRISPR experts and MPN specialists.

4. Additional New Mechanisms of Action.
We continually seek proposals for basic research and preclinical testing of new and innovative mechanisms of action to bring them to the point where other funding options are being directed to these new approaches.

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Caterina

Myelofibrosis (MF)

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