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4 results on '"Huang, Alex C."'

1. Seasonal human coronavirus antibodies are boosted upon SARS-CoV-2 infection but not associated with protection

Author

Anderson, Elizabeth M., primary, Goodwin, Eileen C., additional, Verma, Anurag, additional, Arevalo, Claudia P., additional, Bolton, Marcus J., additional, Weirick, Madison E., additional, Gouma, Sigrid, additional, McAllister, Christopher M., additional, Christensen, Shannon R., additional, Weaver, JoEllen, additional, Hicks, Philip, additional, Manzoni, Tomaz B., additional, Oniyide, Oluwatosin, additional, Ramage, Holly, additional, Mathew, Divij, additional, Baxter, Amy E., additional, Oldridge, Derek A., additional, Greenplate, Allison R., additional, Wu, Jennifer E., additional, Alanio, Cécile, additional, D’Andrea, Kurt, additional, Kuthuru, Oliva, additional, Dougherty, Jeanette, additional, Pattekar, Ajinkya, additional, Kim, Justin, additional, Han, Nicholas, additional, Apostolidis, Sokratis A., additional, Huang, Alex C., additional, Vella, Laura A., additional, Kuri-Cervantes, Leticia, additional, Pampena, M. Betina, additional, Betts, Michael R., additional, Wherry, E. John, additional, Meyer, Nuala J., additional, Cherry, Sara, additional, Bates, Paul, additional, Rader, Daniel J., additional, and Hensley, Scott E., additional

Published
2021
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2. Long-term outcomes of a phase I study of agonist CD40 antibody and CTLA-4 blockade in patients with metastatic melanoma

Author

Bajor, David L., primary, Mick, Rosemarie, additional, Riese, Matthew J., additional, Huang, Alex C., additional, Sullivan, Brendan, additional, Richman, Lee P., additional, Torigian, Drew A., additional, George, Sangeeth M., additional, Stelekati, Erietta, additional, Chen, Fang, additional, Melenhorst, J. Joseph, additional, Lacey, Simon F., additional, Xu, Xiaowei, additional, Wherry, E. John, additional, Gangadhar, Tara C., additional, Amaravadi, Ravi K., additional, Schuchter, Lynn M., additional, and Vonderheide, Robert H., additional

Published
2018
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3. Long-term outcomes of a phase I study of agonist CD40 antibody and CTLA-4 blockade in patients with metastatic melanoma.

Author

Sullivan, Brendan, Richman, Lee P., Chen, Fang, Melenhorst, J. Joseph, Lacey, Simon F., Bajor, David L., Riese, Matthew J., Huang, Alex C., Gangadhar, Tara C., Amaravadi, Ravi K., Schuchter, Lynn M., Vonderheide, Robert H., Mick, Rosemarie, Torigian, Drew A., Wherry, E. John, Xu, Xiaowei, George, Sangeeth M., and Stelekati, Erietta

Subjects
IMMUNE response, MONOCLONAL antibodies, MELANOMA, PATIENTS, COLITIS, CYTOKINE receptors, RADIOTHERAPY, T cells
Abstract

We report long-term clinical outcomes and immune responses observed from a phase 1 trial of agonist CD40 monoclonal antibody (mAb) and blocking CTLA-4 mAb in patients with metastatic melanoma. Twenty-four patients previously untreated with checkpoint blockade were enrolled. The agonistic CD40 mAb CP-870,893 and the CTLA-4 blocking mAb tremelimumab were dosed concomitantly every 3 weeks and 12 weeks, respectively, across four dose combinations. Two patients developed dose-limiting grade 3 immune-mediated colitis that led to the definition of the maximum tolerated dose (MTD). Other immune-mediated toxicity included uveitis (n = 1), hypophysitis (n = 1), hypothyroidism (n = 2), and grade 3 cytokine release syndrome (CRS) (n = 1). The estimated MTD was 0.2 mg/kg of CP-870,893 and 10 mg/kg of tremelimumab. In 22 evaluable patients, the objective response rate (ORR) was 27.3%: two patients (9.1%) had complete responses (CR) and four (18.2%) patients had partial responses (PR). With a median follow-up of 45 months, the median progression-free survival (PFS) was 3.2 months (95% CI, 1.3-5.1 months) and median overall survival (OS) was 23.6 months (95% CI, 11.7-35.5 months). Nine patients are long-term survivors (> 3 years), 8 of whom subsequently received other therapy including PD-1 mAb, surgery, or radiation therapy. Elevated baseline soluble CD25 was associated with shorter OS. Immunologically, treatment was associated with evidence of T cell activation and increased tumor T cell infiltration that was accomplished without therapeutic PD-1/PD-L1 blockade. These results suggest opportunities for immune activation and cancer immunotherapy beyond PD-1. [ABSTRACT FROM AUTHOR]

Published
2018
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4. Seasonal human coronavirus antibodies are boosted upon SARS-CoV-2 infection but not associated with protection.

Author

Anderson EM, Goodwin EC, Verma A, Arevalo CP, Bolton MJ, Weirick ME, Gouma S, McAllister CM, Christensen SR, Weaver J, Hicks P, Manzoni TB, Oniyide O, Ramage H, Mathew D, Baxter AE, Oldridge DA, Greenplate AR, Wu JE, Alanio C, D'Andrea K, Kuthuru O, Dougherty J, Pattekar A, Kim J, Han N, Apostolidis SA, Huang AC, Vella LA, Wherry EJ, Meyer NJ, Cherry S, Bates P, Rader DJ, and Hensley SE

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread within the human population. Although SARS-CoV-2 is a novel coronavirus, most humans had been previously exposed to other antigenically distinct common seasonal human coronaviruses (hCoVs) before the COVID-19 pandemic. Here, we quantified levels of SARS-CoV-2-reactive antibodies and hCoV-reactive antibodies in serum samples collected from 204 humans before the COVID-19 pandemic. We then quantified pre-pandemic antibody levels in serum from a separate cohort of 252 individuals who became PCR-confirmed infected with SARS-CoV-2. Finally, we longitudinally measured hCoV and SARS-CoV-2 antibodies in the serum of hospitalized COVID-19 patients. Our studies indicate that most individuals possessed hCoV-reactive antibodies before the COVID-19 pandemic. We determined that ~23% of these individuals possessed non-neutralizing antibodies that cross-reacted with SARS-CoV-2 spike and nucleocapsid proteins. These antibodies were not associated with protection against SARS-CoV-2 infections or hospitalizations, but paradoxically these hCoV cross-reactive antibodies were boosted upon SARS-CoV-2 infection.

Published
2020
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