Immunotherapy of lymphoma through in situ manipulation of an involved lymph node can allow for development of an active anti-lymphoma immune response without the need for ex vivo handling or immunization with a specific antigen. A comprehensive and successful approach to in situ immunization in lymphoma would require effective presentation of antigen by the lymphoma cells or professional antigenpresenting cells, activation of lymphoma-specific T cells and suppression of the regulatory arm of the immune response to enhance development of a sustained anti-lymphoma T cell response. The current proposal evaluating a novel approach to in situ immunization is based on scientific advances made possible through the UI/MC SPORE over the prior funding period. The overall hypothesis is that in situ immunization with nanoparticles will allow for induction and maintenance of a robust anti-lymphoma immune response with acceptable toxicity. To test this hypothesis, this project will assess the effect of intratumoral injection of nanoparticles (NPs) containing doxorubicin (dox) on lymphoma cells, the immune microenvironment, and the anti-lymphoma immune response in animal models and in a Phase I clinical trial in subjects with lymphoma. It will then assess the effect of intratumoral injection of NPs containing both dox and the toll-like receptor 9 (TLR9) agonist CpG ODN (CpG dox NPs) in mice and humans. Finally, it will assess how agents capable of maintaining the T cell response impact on the success of in situ immunization with NP. Successful development of such an approach to in situ immunization would be of great significance as a way to treat lymphoma, and could be applicable to other cancers as well.

Public Health Relevance

There continues to be a need for new treatments for lymphoma. In situ immunization holds considerable promise as a way to induce a long term, anti-lymphoma immune response that results in clinical benefit for patients. The proposed studies are designed to explore a novel approach to in situ immunization that, if successful, could represent a novel approach to therapy for lymphoma and other cancers.

National Institute of Health (NIH)
National Cancer Institute (NCI)
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University of Iowa
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Link, Brian K (2017) Early Relapse in Follicular Lymphoma: High Risks and High Stakes. J Oncol Pract 13:810-811
Ding, Wei; LaPlant, Betsy R; Call, Timothy G et al. (2017) Pembrolizumab in patients with CLL and Richter transformation or with relapsed CLL. Blood 129:3419-3427
Ammann, Eric M; Shanafelt, Tait D; Larson, Melissa C et al. (2017) Time to Second-line Treatment and Subsequent Relative Survival in Older Patients With Relapsed Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma. Clin Lymphoma Myeloma Leuk 17:e11-e25
Wafa, Emad I; Geary, Sean M; Goodman, Jonathan T et al. (2017) The effect of polyanhydride chemistry in particle-based cancer vaccines on the magnitude of the anti-tumor immune response. Acta Biomater 50:417-427
Paulus, A; Akhtar, S; Yousaf, H et al. (2017) Waldenstrom macroglobulinemia cells devoid of BTKC481S or CXCR4WHIM-like mutations acquire resistance to ibrutinib through upregulation of Bcl-2 and AKT resulting in vulnerability towards venetoclax or MK2206 treatment. Blood Cancer J 7:e565
Tanaka, Yoshimasa; Iwasaki, Masashi; Murata-Hirai, Kaoru et al. (2017) Anti-Tumor Activity and Immunotherapeutic Potential of a Bisphosphonate Prodrug. Sci Rep 7:5987
Wang, Xueju; Dasari, Surendra; Nowakowski, Grzegorz S et al. (2017) Retinoic acid receptor alpha drives cell cycle progression and is associated with increased sensitivity to retinoids in T-cell lymphoma. Oncotarget 8:26245-26255
Scott, David W; Abrisqueta, Pau; Wright, George W et al. (2017) New Molecular Assay for the Proliferation Signature in Mantle Cell Lymphoma Applicable to Formalin-Fixed Paraffin-Embedded Biopsies. J Clin Oncol 35:1668-1677
Tracy, S I; Maurer, M J; Witzig, T E et al. (2017) Vitamin D insufficiency is associated with an increased risk of early clinical failure in follicular lymphoma. Blood Cancer J 7:e595
Law, Philip J; Berndt, Sonja I; Speedy, Helen E et al. (2017) Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia. Nat Commun 8:14175

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