A Phase Ib Study of Preoperative, Locoregional IRX-2 Cytokine Immunotherapy to Prime Immune Responses in Patients with Early-Stage Breast Cancer
| Autor: | Valerie Conrad, Staci Mellinger, Walter J. Urba, Amanda Y. Seino, James H. Imatani, Shaghayegh Aliabadi-Wahle, Kelly Shea Perlewitz, Joanna Pucilowska, Monil Shah, Alison Conlin, Venkatesh Rajamanickam, Shu-Ching Chang, Dottie Waddell, Yaping Wu, Zhaoyu Sun, Deborah Laxague, Anupama K. Acheson, Martiza Martel, William L. Redmond, Katherine Sanchez, David B. Page, Nicole Moxon |
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| Rok vydání: | 2019 |
| Předmět: |
Oncology
Cancer Research medicine.medical_specialty Cyclophosphamide medicine.medical_treatment Breast Neoplasms Pilot Projects Preoperative care B7-H1 Antigen 03 medical and health sciences 0302 clinical medicine Breast cancer Lymphocytes Tumor-Infiltrating Internal medicine Preoperative Care medicine Biomarkers Tumor Humans Aged Cytokine Therapy business.industry Lumpectomy Immunity Immunotherapy Middle Aged medicine.disease Regimen Treatment Outcome 030220 oncology & carcinogenesis Cytokines Female Patient Safety business Mastectomy 030215 immunology medicine.drug |
| Zdroj: | Clinical cancer research : an official journal of the American Association for Cancer Research. 26(7) |
| ISSN: | 1557-3265 |
| Popis: | Purpose: To evaluate the safety and feasibility of preoperative locoregional cytokine therapy (IRX-2 regimen) in early-stage breast cancer, and to evaluate for intratumoral and peripheral immunomodulatory activity. Patients and Methods: Sixteen patients with stage I–III early-stage breast cancer (any histology type) indicated for surgical lumpectomy or mastectomy were enrolled to receive preoperative locoregional immunotherapy with the IRX-2 cytokine biological (2 mL subcutaneous × 10 days to periareolar skin). The regimen also included single-dose cyclophosphamide (300 mg/m2) on day 1 to deplete T-regulatory cells and oral indomethacin to modulate suppressive myeloid subpopulations. The primary objective was to evaluate feasibility (i.e., receipt of therapy without surgical delays or grade 3/4 treatment–related adverse events). The secondary objective was to evaluate changes in stromal tumor–infiltrating lymphocyte score. The exploratory objective was to identify candidate pharmacodynamic changes for future study using a variety of assays, including flow cytometry, RNA and T-cell receptor DNA sequencing, and multispectral immunofluorescence. Results: Preoperative locoregional cytokine administration was feasible in 100% (n = 16/16) of subjects and associated with increases in stromal tumor–infiltrating lymphocytes (P < 0.001). Programmed death ligand 1 (CD274) was upregulated at the RNA (P < 0.01) and protein level [by Ventana PD-L1 (SP142) and immunofluorescence]. Other immunomodulatory effects included upregulation of RNA signatures of T-cell activation and recruitment and cyclophosphamide-related peripheral T-regulatory cell depletion. Conclusions: IRX-2 is safe in early-stage breast cancer. Potentially favorable immunomodulatory changes were observed, supporting further study of IRX-2 in early-stage breast cancer and other malignancies. |
| Databáze: | OpenAIRE |
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