Target Grants: Request for Proposals

Target Grants: Request for Proposals is sponsored by amfAR, The Foundation for AIDS Research. amfAR's Target Grants offer funding for impactful HIV cure research, supporting both clinical and pre-clinical proposals. The program aims to advance scientific understanding and drive medical breakthroughs in areas of unmet medical need related to HIV.

Target Grants: Request for Proposals - amfAR, The Foundation for AIDS Research Target Grants: Request for Proposals Therapeutic Immune Reprogramming in Cancer: Targeting Dysfunctional, Suppressive, and Senescent Immune States Award Amount and Performance Period Award amount: Up to $480,000, including up to 20% indirect costs Performance period: November 1, 2026 – October 31, 2028 Historically, amfAR’s research initiatives have focused on finding a cure for HIV.

Four decades of HIV research have reshaped our understanding of the immune system, and insights from HIV have been leveraged in adjacent fields, including cancer immunology. Innovation can be bi-directional and reciprocal. Seminal findings in cancer immunology have also furthered understanding of HIV biology.

To facilitate this reciprocal innovation, amfAR seeks proposals that investigate strategies to reprogram dysfunctional, suppressive, senescent, or otherwise ineffective immune states in cancer .

More specifically, this Request for Proposals (RFP) is intended to support mechanistic, preclinical, and translational studies that test how anti-tumor immunity can be restored, redirected, or amplified in cancers shaped by chronic antigen exposure, viral oncogenesis, immune dysfunction, or highly immunogenic tumor biology.

Cancer immunotherapy has transformed treatment for many malignancies, yet durable responses remain limited by persistent immune exhaustion, suppressive myeloid programs, impaired antigen presentation, immune exclusion, stromal barriers, and tissue niches that maintain dysfunctional cell states.

It is critical to move beyond descriptive profiling and test interventions capable of changing immune-cell state or tumor microenvironment function.

Responsive projects may use a range of immune-reprogramming strategies, including but not limited to: RNA-based technologies, targeted delivery platforms, cytokine or chemokine modulation, epigenetic or transcriptional perturbation, engineered immune-cell approaches, antibody- or ligand-directed immune modulation, organoid or explant-based perturbation systems, and computationally guided target discovery.

Application Process and Deadlines The amfAR Research Department verifies applicants’ eligibility and reviews synopses based on relevance, potential impact, and alignment with amfAR’s mission. A selected number of applicants will be invited to submit a full application . We regret that we are unable to discuss every submission with applicants.

All invited applications are evaluated and scored through external peer – review process .

Responsive applications may focus on one or more of the following areas: Reversal of dysfunctional or senescent immune states Studies that test strategies to reverse, bypass, or remodel exhausted, senescent, suppressed, or terminally dysfunctional conventional or non-conventional T cells, NK cells, B cells, dendritic cells, macrophages, or other immune populations in cancer.

Reprogramming suppressive tumor microenvironments Studies that target myeloid suppression, immune exclusion, stromal barriers, cytokine and chemokine circuits, impaired antigen presentation, regulatory immune populations, or other mechanisms that prevent productive anti-tumor immunity.

Selective expansion, recruitment, or activation of anti-tumor immune populations Studies that identify and test methods to evaluate, expand, recruit, activate, or redirect immune-cell populations with anti-tumor activity.

RNA-enabled and other targeted immune-modulatory approaches Studies using mRNA, self-amplifying RNA, circular RNA, siRNA, antisense oligonucleotides, RNA-guided perturbation systems, lipid nanoparticles, targeted delivery vehicles, or related platforms to modulate immune-cell state or tumor microenvironment function.

Epigenetic, transcriptional, or metabolic immune reprogramming Studies that target durable cell-state programs that lock immune cells into dysfunctional, suppressive, or non-productive states.

Perturbation screens and target discovery Studies using CRISPR, RNA-based perturbation, pooled genetic screens, chemical biology, single-cell perturb-seq, spatial perturbation systems, or computational modeling to identify actionable immune-reprogramming targets.

Human-relevant models of immune reprogramming Studies using patient-derived organoids, tumor–immune co-cultures, tumor slice cultures, lymphoid organoids, humanized models, or ex vivo human tumor systems to test immune-reprogramming mechanisms.

Combination immunotherapy strategies Studies testing immune reprogramming in combination with checkpoint blockade, therapeutic vaccination, adoptive cell therapy, antibodies, radiation, targeted therapy, or other cancer treatments, provided that the immune-reprogramming mechanism is central to the proposal.

Projects may address cancers in which immune dysfunction, chronic antigen exposure, viral antigen expression, inflammation, or immunogenic tumor biology create a strong rationale for immune reprogramming or functional enhancement.

Examples include, but are not limited to: HPV-associated cancers, including anal, cervical, oropharyngeal, vulvar, vaginal, and penile cancers EBV-associated lymphomas and other EBV-associated malignancies KSHV/HHV-8-associated malignancies, including Kaposi sarcoma and primary effusion lymphoma HBV- or HCV-associated liver cancer HTLV-1 associated malignancies Lung or colorectal cancers, particularly studies focused on immune dysfunction, antigen presentation, or myeloid-mediated suppression Immunogenic hematologic malignancies, including myeloma, when the project has a clear immune-reprogramming rationale The proposed research must be conducted or validated either in vivo , in humans or disease-relevant animal models or ex vivo , in disease-relevant cells or tissues of either animal or human origin.

Interventions tested exclusively in cell lines or in “healthy” primary cells will not be considered responsive to this RFP. Priority will be given to proposals that define a specific immune dysfunction state, nominate a clear reprogramming strategy, and test whether that strategy restores or enhances anti-tumor immune function in a cancer-relevant model.

Valuable outputs could include Biomarkers predictive of immune response Datasets that define cell state trajectories Computational methods, including those leveraging Artificial intelligence/Machine Learning approaches, that facilitate interpretation of dynamic immune states Biological targets relevant to immune dysfunction and rescue Highly translational human models.

Synopsis submission deadline : June 29, 2026, 3 PM (ET) Invitation to submit full grant application: July 13, 2026 Deadline to submit full application: August 24, 2026, 3 PM (ET) Any biomedical researcher holding a research or clinical doctoral degree who is affiliated with a nonprofit research institution, anywhere in the world, is eligible to apply.

To provide additional information and answer questions, amfAR hosted an informational webinar. View its recording here . For more information about this Target Grant call, please see our Frequently Asked Questions .

Future requests for proposals