Current major areas of research focus include:

Modifying the tumor microenvironment to enhance the anti-tumor immune response

Dr. Weiner and colleagues are exploring the effects of TLR agonists on the tumor microenvironment with the goal of enhancing the anti-tumor immune response. The laboratory performed many of the preclinical studies exploring a variety of such agents including the virus-like particle continuing a TLR9 agonist now known as vidutolimod. Vidutolimod has now shown considerable promise in early phase clinical trials with the Holden Comprehensive Cancer Center playing a central role. The Weiner laboratory continues to conduct in vitro studies, animal model evaluation and correlative analysis of clinical biospecimens.  This extends from the study of basic mechanisms of immune activation through evaluation of novel agents to assessment of samples obtained from patients on clinical trials.  These studies are done in collaboration with a number of scientists at Iowa and around the country including Drs. Gregory Fitzpatrick, Aliasger Salem, Andrean Simons-Burnett, Carlos Chan and Arthur Krieg.  This research is supported in part by Zola Pharmaceuticals and a University of Iowa Carver College of Medicine GAP Award.

• Select publications from the Weiner lab in this area of focus
  • Weiner GJ, Liu HM, Wooldridge JE, Dahle CE, Krieg AM. Immunostimulatory oligodeoxynucleotides containing the CpG motif are effective as immune adjuvants in tumor antigen immunization. Proceedings of the National Academy of Sciences of the United States of America. 1997;94(20):10833-7. PubMed PMID: 9380720; PubMed Central PMCID: PMC23500.
  • Hartmann G, Weiner GJ, Krieg AM. CpG DNA: a potent signal for growth, activation, and maturation of human dendritic cells. Proceedings of the National Academy of Sciences of the United States of America. 1999;96(16):9305-10. PubMed PMID: 10430938; PubMed Central PMCID: PMC17777.
  • Lemke-Miltner CD, Blackwell SE, Yin C, Krug AE, Morris AJ, Krieg AM, Weiner GJ. Antibody Opsonization of a TLR9 Agonist-Containing Virus-like Particle Enhances In Situ Immunization. J Immunol. 2020 Mar 1;204(5):1386-1394. doi:10.4049/jimmunol.1900742. Epub 2020 Jan 17. PMID: 31953355; PMCID: PMC7033003.
  • Sabree SA, Voigt AP, Blackwell SE, Vishwakarma A, Chimenti MS, Salem AK, Weiner GJ. Direct and indirect immune effects of CMP-001, a virus-like particle containing a TLR9 agonist. J Immunother Cancer. 2021;9(6). Epub 2021/06/05. doi: 10.1136/jitc-2021-002484. PMCID: PMC8183212 

Mechanisms of action of anti-cancer monoclonal antibodies

The Weiner Laboratory has a long-standing interest in the mechanisms of action of anti-cancer antibodies including both monospecific and bispecific antibodies. The laboratory is exploring mechanisms of synergy between monoclonal antibody and bispecific antibody approaches to cancer therapy.  The goal of this research is to identify approaches to designing more effective anti-cancer monoclonal antibody treatment regimens. This research is supported in part by a grant from the V Foundation and is being done in collaboration with a number of colleagues including Drs Umar Farooq and Nanmeng Yu.

• Select publications from the Weiner lab on this area of focus
  • Weiner GJ, Kostelny SA, Hillstrom JR, Cole MS, Link BK, Wang SL, Tso JY. The role of T cell activation in anti-CD3 x antitumor bispecific antibody therapy. Journal of immunology. 1994;152(5):2385-92. PubMed PMID: 8133049
  • Veeramani S, Wang SY, Dahle C, Blackwell S, Jacobus L, Knutson T, Button A, Link BK, Weiner GJ. Rituximab infusion induces NK activation in lymphoma patients with the high-affinity CD16 polymorphism. Blood. 2011;118(12):3347-9. doi: 10.1182/blood-2011-05-351411. PubMed PMID: 21768303; PubMed Central PMCID: PMC3179401.
  • Weiner GJ. Building better monoclonal antibody-based therapeutics. Nat Rev Cancer. 2015 Jun;15(6):361-70. doi: 10.1038/nrc3930. Review. PubMed PMID:25998715; PubMed Central PMCID: PMC4491443.
  • Wang Z, Chimenti MS, Strouse C, Weiner GJ. T cells, particularly activated CD4(+) cells, maintain anti-CD20-mediated NK cell viability and antibody dependent cellular cytotoxicity. Cancer Immunol Immunother. 2021. Epub 2021/06/11. doi: 10.1007/s00262-021-02976-7. PubMed PMID: 34110453.
  • Arora J, Ayyappan S, Yin C, Smith BJ, Lemke-Miltner CD, Wang Z, Farooq U, Weiner GJ: T cell help in the tumor microenvironment enhances rituximab-mediated NK cell ADCC.  Blood.  143(18): 1816-24.  2024. Pubmed PMID: 38457360.

Measuring receptor occupancy by ligands

Dr. Weiner, in collaboration Dr. Suresh Veeramani, an Assistant Research Professor in Dr. Weiner’s group, has developed a novel bioassay platform, based on RNA aptamers, that can be used to quantify the fraction of receptors occupied by ligands. This concept has been explored most extensively with IL2-CD25 and PD1-PDL1. The biologic and potential clinical significance of being able to quantify the “fractional occupancy” of receptors by their ligands is currently under evaluation in the laboratory.

• Select publications from the Weiner lab in this area of focus
  • Veeramani S, Blackwell SE, Thiel WH, Yang ZZ, Ansell SM, Giangrande PH, Weiner GJ. An RNA Aptamer-Based Biomarker Platform Demonstrates High Soluble CD25 Occupancy by IL2 in the Serum of Follicular Lymphoma Patients. Cancer Immunol Res. 2019 Sep;7(9):1511-1522. doi: 10.1158/2326-6066.CIR-18-0821. Epub 2019 Aug 5. PubMed PMID: 31383650; PubMed Central PMCID: PMC6726511.
  • Veeramani S, Weiner GJ. Quantification of Receptor Occupancy by Ligand-An Understudied Class of Potential Biomarkers. Cancers (Basel). 2020;12(10). Epub 2020/10/18. doi: 10.3390/cancers12102956. PubMed PMID: 33066142; PMCID: PMC7601969.

Modifying macrophage polarization to enhance the anti-tumor immune response.

Dr. Weiner is collaborating with a team led by Dr. Jill Kolesar , Dean of the College of Pharmacy at the University of Iowa, to assess the effect of Macrophage-generated Extracellular Vesicles on macrophage polarization with the goal of enhancing the anti-tumor response in ovarian cancer.  This research is supported by ARPA-H.