Takuya Osada

Positions:

Associate Professor in Surgery

Surgery, Surgical Sciences
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 1986

University of Tokyo (Japan)

Ph.D. 1997

University of Tokyo (Japan)

Grants:

Developing a HER3 Vaccine to Prevent Resistance to Endocrine Therapy

Administered By
Surgery, Surgical Sciences
Awarded By
Department of Defense
Role
Co Investigator
Start Date
End Date

Targeting the WNT/beta-catenin Pathway in Triple Negative Breast Cancer

Administered By
Medicine, Medical Oncology
Awarded By
Department of Defense
Role
Investigator
Start Date
End Date

Detection and Elimination of Oncogenic Signaling Networks in Pre-malignant and Malignant Cells with Magnetic Resonance Imaging

Administered By
Surgery, Surgical Sciences
Awarded By
Department of Defense
Role
Co Investigator
Start Date
End Date

Targeting hCG-beta for Breast Cancer Immunotherapy

Administered By
Duke Cancer Institute
Awarded By
National Institutes of Health
Role
Research Analyst
Start Date
End Date

Dendritic Cell Mobilization and Active Immunotherapy

Administered By
Surgery, Surgical Sciences
Awarded By
National Institutes of Health
Role
Investigator
Start Date
End Date

Publications:

Targeting the glucagon receptor signaling pathway as a novel strategy to counteract PI3K inhibitor induced hyperglycemia while sustaining tumor PI3K inhibition.

Authors
Wang, J; Osada, T; Morse, MA; Calzone, F; Yan, H; Thai, D; Lyerly, HK
MLA Citation
Wang, Jie, et al. “Targeting the glucagon receptor signaling pathway as a novel strategy to counteract PI3K inhibitor induced hyperglycemia while sustaining tumor PI3K inhibition.Leuk Lymphoma, vol. 62, no. 7, July 2021, pp. 1761–64. Pubmed, doi:10.1080/10428194.2021.1881504.
URI
https://scholars.duke.edu/individual/pub1474786
PMID
33576297
Source
pubmed
Published In
Leuk Lymphoma
Volume
62
Published Date
Start Page
1761
End Page
1764
DOI
10.1080/10428194.2021.1881504

Intratumoral Plasmid IL12 Expands CD8<sup>+</sup> T Cells and Induces a CXCR3 Gene Signature in Triple-negative Breast Tumors that Sensitizes Patients to Anti-PD-1 Therapy.

<h4>Purpose</h4>Triple-negative breast cancer (TNBC) is an aggressive disease with limited therapeutic options. Antibodies targeting programmed cell death protein 1 (PD-1)/PD-1 ligand 1 (PD-L1) have entered the therapeutic landscape in TNBC, but only a minority of patients benefit. A way to reliably enhance immunogenicity, T-cell infiltration, and predict responsiveness is critically needed.<h4>Patients and methods</h4>Using mouse models of TNBC, we evaluate immune activation and tumor targeting of intratumoral IL12 plasmid followed by electroporation (tavokinogene telseplasmid; Tavo). We further present a single-arm, prospective clinical trial of Tavo monotherapy in patients with treatment refractory, advanced TNBC (OMS-I140). Finally, we expand these findings using publicly available breast cancer and melanoma datasets.<h4>Results</h4>Single-cell RNA sequencing of murine tumors identified a CXCR3 gene signature (CXCR3-GS) following Tavo treatment associated with enhanced antigen presentation, T-cell infiltration and expansion, and PD-1/PD-L1 expression. Assessment of pretreatment and posttreatment tissue from patients confirms enrichment of this CXCR3-GS in tumors from patients that exhibited an enhancement of CD8<sup>+</sup> T-cell infiltration following treatment. One patient, previously unresponsive to anti-PD-L1 therapy, but who exhibited an increased CXCR3-GS after Tavo treatment, went on to receive additional anti-PD-1 therapy as their immediate next treatment after OMS-I140, and demonstrated a significant clinical response.<h4>Conclusions</h4>These data show a safe, effective intratumoral therapy that can enhance antigen presentation and recruit CD8 T cells, which are required for the antitumor efficacy. We identify a Tavo treatment-related gene signature associated with improved outcomes and conversion of nonresponsive tumors, potentially even beyond TNBC.
Authors
Telli, ML; Nagata, H; Wapnir, I; Acharya, CR; Zablotsky, K; Fox, BA; Bifulco, CB; Jensen, SM; Ballesteros-Merino, C; Le, MH; Pierce, RH; Browning, E; Hermiz, R; Svenson, L; Bannavong, D; Jaffe, K; Sell, J; Foerter, KM; Canton, DA; Twitty, CG; Osada, T; Lyerly, HK; Crosby, EJ
MLA Citation
Telli, Melinda L., et al. “Intratumoral Plasmid IL12 Expands CD8+ T Cells and Induces a CXCR3 Gene Signature in Triple-negative Breast Tumors that Sensitizes Patients to Anti-PD-1 Therapy.Clinical Cancer Research : An Official Journal of the American Association for Cancer Research, vol. 27, no. 9, May 2021, pp. 2481–93. Epmc, doi:10.1158/1078-0432.ccr-20-3944.
URI
https://scholars.duke.edu/individual/pub1474844
PMID
33593880
Source
epmc
Published In
Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Volume
27
Published Date
Start Page
2481
End Page
2493
DOI
10.1158/1078-0432.ccr-20-3944

Long-term survival of patients with stage III colon cancer treated with VRP-CEA(6D), an alphavirus vector that increases the CD8+ effector memory T cell to Treg ratio.

BACKGROUND: There remains a significant need to eliminate the risk of recurrence of resected cancers. Cancer vaccines are well tolerated and activate tumor-specific immune effectors and lead to long-term survival in some patients. We hypothesized that vaccination with alphaviral replicon particles encoding tumor associated antigens would generate clinically significant antitumor immunity to enable prolonged overall survival (OS) in patients with both metastatic and resected cancer. METHODS: OS was monitored for patients with stage IV cancer treated in a phase I study of virus-like replicon particle (VRP)-carcinoembryonic antigen (CEA), an alphaviral replicon particle encoding a modified CEA. An expansion cohort of patients (n=12) with resected stage III colorectal cancer who had completed their standard postoperative adjuvant chemotherapy was administered VRP-CEA every 3 weeks for a total of 4 immunizations. OS and relapse-free survival (RFS) were determined, as well as preimmunization and postimmunization cellular and humoral immunity. RESULTS: Among the patients with stage IV cancer, median follow-up was 10.9 years and 5-year survival was 17%, (95% CI 6% to 33%). Among the patients with stage III cancer, the 5-year RFS was 75%, (95%CI 40% to 91%); no deaths were observed. At a median follow-up of 5.8 years (range: 3.9-7.0 years) all patients were still alive. All patients demonstrated CEA-specific humoral immunity. Patients with stage III cancer had an increase in CD8 +TEM (in 10/12) and decrease in FOXP3 +Tregs (in 10/12) following vaccination. Further, CEA-specific, IFNγ-producing CD8+granzyme B+TCM cells were increased. CONCLUSIONS: VRP-CEA induces antigen-specific effector T cells while decreasing Tregs, suggesting favorable immune modulation. Long-term survivors were identified in both cohorts, suggesting the OS may be prolonged.
Authors
Crosby, EJ; Hobeika, AC; Niedzwiecki, D; Rushing, C; Hsu, D; Berglund, P; Smith, J; Osada, T; Gwin Iii, WR; Hartman, ZC; Morse, MA; Lyerly, HK
MLA Citation
Crosby, Erika J., et al. “Long-term survival of patients with stage III colon cancer treated with VRP-CEA(6D), an alphavirus vector that increases the CD8+ effector memory T cell to Treg ratio.J Immunother Cancer, vol. 8, no. 2, Nov. 2020. Pubmed, doi:10.1136/jitc-2020-001662.
URI
https://scholars.duke.edu/individual/pub1464810
PMID
33177177
Source
pubmed
Published In
Journal for Immunotherapy of Cancer
Volume
8
Published Date
DOI
10.1136/jitc-2020-001662

Heat shock protein 90-targeted photodynamic therapy enables treatment of subcutaneous and visceral tumors.

Photodynamic therapy (PDT) ablates malignancies by applying focused near-infrared (nIR) light onto a lesion of interest after systemic administration of a photosensitizer (PS); however, the accumulation of existing PS is not tumor-exclusive. We developed a tumor-localizing strategy for PDT, exploiting the high expression of heat shock protein 90 (Hsp90) in cancer cells to retain high concentrations of PS by tethering a small molecule Hsp90 inhibitor to a PS (verteporfin, VP) to create an Hsp90-targeted PS (HS201). HS201 accumulates to a greater extent than VP in breast cancer cells both in vitro and in vivo, resulting in increased treatment efficacy of HS201-PDT in various human breast cancer xenografts regardless of molecular and clinical subtypes. The therapeutic index achieved with Hsp90-targeted PDT would permit treatment not only of localized tumors, but also more diffusely infiltrating processes such as inflammatory breast cancer.
Authors
Kaneko, K; Osada, T; Morse, MA; Gwin, WR; Ginzel, JD; Snyder, JC; Yang, X-Y; Liu, C-X; Diniz, MA; Bodoor, K; Hughes, PF; Haystead, TA; Lyerly, HK
MLA Citation
Kaneko, Kensuke, et al. “Heat shock protein 90-targeted photodynamic therapy enables treatment of subcutaneous and visceral tumors.Commun Biol, vol. 3, no. 1, May 2020, p. 226. Pubmed, doi:10.1038/s42003-020-0956-7.
URI
https://scholars.duke.edu/individual/pub1441154
PMID
32385408
Source
pubmed
Published In
Communications Biology
Volume
3
Published Date
Start Page
226
DOI
10.1038/s42003-020-0956-7

Abstract 4071: A novel combination therapy of high intensity focused ultrasound and PDL1 blockades against advanced breast cancer

Authors
Abe, S; Osada, T; Kaneko, K; Zhong, P; Lyerly, HK
MLA Citation
Abe, Shinya, et al. “Abstract 4071: A novel combination therapy of high intensity focused ultrasound and PDL1 blockades against advanced breast cancer.” Immunology, American Association for Cancer Research, 2019. Crossref, doi:10.1158/1538-7445.am2019-4071.
URI
https://scholars.duke.edu/individual/pub1416574
Source
crossref
Published In
Immunology
Published Date
DOI
10.1158/1538-7445.am2019-4071