A5072721121- Immunotherapy and Immune Responses
- Cancer Immunotherapy and Biomarkers
- CAR-T cell therapy research
- Cell Adhesion Molecules Research
- Immune Cell Function and Interaction
- Histone Deacetylase Inhibitors Research
- Chemokine receptors and signaling
- Salivary Gland Tumors Diagnosis and Treatment
- RNA Interference and Gene Delivery
- Lung Cancer Diagnosis and Treatment
- Cancer Cells and Metastasis
- Brain Metastases and Treatment
- Immune cells in cancer
- vaccines and immunoinformatics approaches
- Monoclonal and Polyclonal Antibodies Research
- Esophageal Cancer Research and Treatment
- Phagocytosis and Immune Regulation
Massachusetts Institute of Technology
2023-2024
University of California, San Diego
2022-2024
Allen Institute
2024
La Jolla Alcohol Research
2022
UC San Diego Health System
2022
Despite the promise of immune checkpoint inhibition (ICI), therapeutic responses remain limited. This raises possibility that standard care treatments delivered in concert may compromise tumor response. To address this, we employ tobacco-signature head and neck squamous cell carcinoma murine models which map tumor-draining lymphatics develop for regional lymphablation with surgery or radiation. We find eliminates ICI response, worsening overall survival repolarizing tumor- peripheral-immune...
Systemically administered cytokines are potent immunotherapeutics but can cause severe dose-limiting toxicities. To overcome this challenge, have been engineered for intratumoral retention after local delivery. However, despite inducing regression of treated lesions, tumor-localized often elicit only modest responses at distal untreated tumors. In the present study, we report a localized cytokine therapy that safely elicits systemic antitumor immunity by targeting ubiquitous leukocyte...
Abstract Immune checkpoint inhibition has demonstrated no benefit when combined with chemoradiotherapy for locally advanced HNSCC, raising the possibility that standard therapies compromise response to immunotherapy. To address this hypothesis, we previously ablating tumor draining lymphatics abolishes immune-oncology therapy. Specifically, defined immunotherapy is coordinated by interferon type-I signaling through cDC1 population in tumor-draining lymph nodes. These findings support premise...
Abstract Immune checkpoint inhibition has demonstrated no benefit when combined with chemoradiotherapy for locally advanced HNSCC, raising the possibility that standard therapies compromise response to immunotherapy. To address this hypothesis, we previously ablating tumor draining lymphatics abolishes immune-oncology therapy. Specifically, defined immunotherapy is coordinated by interferon type-I signaling through cDC1 population in tumor-draining lymph nodes. These findings support premise...
Abstract Cytokine therapies are potent immunotherapy agents but exhibit severe dose-limiting toxicities. One strategy to overcome this involves engineering cytokines for intratumoral retention following local delivery. Here, we develop a localized cytokine therapy that elicits profound anti-tumor immunity by engineered targeting the ubiquitous leukocyte receptor CD45. We designed CD45-targeted immunocytokines (αCD45-Cyt) that, upon injection, decorated surface of leukocytes in tumor and...
<h3>Background</h3> Head and neck squamous cell carcinomas (HNSCCs) represent the sixth most common cancer worldwide with an estimated 65,630 cases 14,500 deaths in United States last year. Fortuitously, by virtue of their high mutational burden robust neoantigenome, HNSCCs harbor abundance tumor-specific antigen (TSA)-T cells; and, thus, ideal target for autologous adoptive therapy. However, lack a reliable biomarker to accurately identify bona fide TSA-T cells among heterogenous population...
6060 Background: Head and neck squamous cell carcinoma (HNSCC) is a lethal malignancy comprises two distinct etiology: human papillomavirus (HPV)+ve -ve. Marijuana use associated with HPV+ oropharyngeal infection conflicting data show positive negative associations of daily marijuana tobacco-associated HPV- HNSCC. However, cannabinoid continues to increase in the US general population for recreational purposes as well cancer patients palliative care. G-protein coupled receptors (GPCRs),...
Abstract Immune checkpoint inhibition (ICI) with anti-CTLA-4 and anti-PD-1 has revolutionized oncology; however, response rates remain limited in most cancer types, highlighting the need for more effective immune oncology (IO) treatment strategies. Paradoxically, head neck squamous cell carcinoma (HNSCC), which bears a mutational burden infiltrate commensurate cancers that respond robustly to ICI, demonstrated no anti- CTLA-4 any setting or locally-advanced disease. Scrutiny of landmark...
<h3>Background</h3> PD-1 inhibition (PD1i) has demonstrated no benefit for locally advanced HNSCC, and emerging neoadjuvant PD1i window of opportunity trial data yield promising but limited responses. Our previous work demonstrates that ablating tumor draining lymphatics compromises the response to immune-oncology therapy.<sup>1</sup> In concert, a recently completed phase I investigating immunoradiotherapy (IRT) treatment-naïve HNSCC 60% major pathologic 100% clinical-to-pathologic...
<h3>Background</h3> Myeloid antigen presenting cells (APCs) are critical to PD-1 inhibition (PD1i) and radiotherapy responses in Head Neck Squamous Cell Carcinoma (HNSCC), but inhibited by the 'don't eat me' immune checkpoint molecule CD47 overexpressed on tumor that interacts with SIRPα receptor found myeloid cells, impeding their function. Evorpacept is a high affinity blocking fusion protein binding domain coupled an inactive Fc avoids anemia hematologic toxicities. We hypothesize...
<h3>Background</h3> While immune checkpoint inhibitor (ICI) therapy has demonstrated remarkable efficacy for treating cancers, achieving complete and durable immunity memory to prevent tumor recurrence remains elusive. Understanding the mechanisms of immunologic after responses ICI is essential optimizing treatment achieve sustained anticancer responses.<sup>1</sup> This study aimed investigate long-lasting induced by in an orthotopic murine model tobacco-signature head neck cancer (HNC) –...