lab scene

The Weiner laboratory currently has three major areas of focus:

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

Dr. Weiner and colleagues are exploring the effects of the TLR9 agonist CpG ODN in a variety of approaches. The laboratory performed many of the preclinical studies demonstrating the mechanisms of action and therapeutic potential of a virus-like particle contining 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 explore mechanisms of action vidutolimod and related novel virus-like particles as immunotherapeutic agents. This includes in vitro studies, animal models and correlative analysis of samples obtained from patients on clinical trials. These studies are being done in close collaboration with Drs. Aliasger Salem, Carlos Chan, Ann Simons-Burnett and Umar Farooq at the University of Iowa as well as with Regeneron Pharmaceuticals.

  • Older publications from the Weiner lab on 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.
  • Recent publications
    • 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. The goal of this research is to identify approaches to designing more effective anti-cancer monoclonal antibody treatment regimens. Most recently, the laboratory has identified T cell help as being important in maintaining the ability of Natural Killer cells to mediate antibody dependent cellular cytotoxicity. The laboratory has preliminary evidence that concurrent treatment with monoclonal antibodies and bispecific antibodies that activate T cells in the tumor microenvironment may enhance T cell help and so make both types of antibodies more effective. This concept is now being tested in animal models and is expected to advance to clinical evaluation shortly.

  • Older 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.
  • Recent publications
    • 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.
    • Wang Z, Yin C, Lum LG, Simons A, Weiner GJ. Bispecific antibody-activated T cells enhance NK cell-mediated antibody-dependent cellular cytotoxicity. J Hematol Oncol. 2021;14(1):204. PMCID: PMC8656063

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.

  • Recent publications
    • 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.