![](http://investorshub.advfn.com/images/default_ih_profile2_4848.jpg?cb=0)
Saturday, March 26, 2016 8:22:49 PM
Parent Project Number: 2P50CA136393-06A1 Sub-Project ID: 7026 Contact PI / Project Leader: KNUTSON, KEITH L
Title: PROJECT 8 - TH17 DENDRITIC CELL VACCINE Awardee Organization: MAYO CLINIC ROCHESTER
Abstract Text:
PROJECT SUMMARY – Project 8 The host immune response to ovarian cancer (OvCa) has been repeatedly demonstrated and has a dramatic association with survival; however, for the majority of patients, immune control of OvCa is temporary, and the tumor cells persist, grow, and ultimately lead to patient death. We and others have shown that this ability of OvCa to evade host immune responses is due in large part to the influence of regulatory T cells (Tregs) and suppressive myeloid cells. Both Tregs and suppressive myeloid cells cause anergy of OvCa-reactive T helper 1 (Th1) and CD8 T cells. Tregs are induced not only during endogenous anti-OvCa immune responses, but also in the context of anti-OvCa immunotherapies, thereby limiting efficacy. Multiple groups have made efforts to target suppressor cells in OvCa using chemotherapy agents and toxins, but the effects of these agents are transient and can also deplete beneficial cell types. In contrast, T helper 17 (Th17) cells have been demonstrated to downregulate these suppressor cells while simultaneously promoting a proinflammatory antigen-specific immune response. We have recently described a novel strategy of ex vivo DC maturation that leads to a robust antigen-specific Th17 response. In a model of OvCa, mice treated with Th17-inducing DCs demonstrated robust anti-OvCa Th17 immune responses, a dramatic reduction in Tregs, and durable OvCa remissions. In addition to our studies demonstrating the promise of generating Th17 immune responses using DCs matured ex vivo, we have also identified a novel OvCa antigen, the folate receptor alpha (FRa). This protein is overexpressed on the vast majority of human (and mouse) OvCa tumors and is linked to worse clinical outcomes. We have, therefore, identified antigenic peptides from FRa and completed a clinical study testing these peptides in a therapeutic vaccine. Building on these results, we propose to 1) identify the immune effectors underpinning the anti-tumor efficacy of Th17-inducing cancer vaccines, 2) determine whether the induction of Th17 immune responses targeting ovarian cancer antigens will overcome local tumor immune suppression by inhibiting Treg generation and modulating infiltrating myeloid cell function, and 3) perform a phase 1 clinical trial to determine whether FRa-specific Th17 T cell responses can be safely generated in OvCa patients following conventional therapy. Collectively, these aims will help elucidate the mechanisms by which Th17-inducing DC vaccination suppresses tumor growth, and will provide an assessment of safety and immunogenicity of this strategy for human OvCa patients, fostering the continuation of a Mayo SPORE program of innovative immune-based approaches for preventing disease recurrence in OvCa.
Cancer Res. 2016 Jan 15;76(2):239-50. doi: 10.1158/0008-5472.CAN-15-0748. Epub 2015 Nov 13.
PD-1 Blunts the Function of Ovarian Tumor-Infiltrating Dendritic Cells by Inactivating NF-?B.
Karyampudi L1, Lamichhane P2, Krempski J3, Kalli KR4, Behrens MD3, Vargas DM3, Hartmann LC4, Janco JM5, Dong H3, Hedin KE3, Dietz AB6, Goode EL7, Knutson KL8.
Abstract:
The PD-1:PD-L1 immune signaling axis mediates suppression of T-cell-dependent tumor immunity. PD-1 expression was recently found to be upregulated on tumor-infiltrating murine (CD11c(+)CD11b(+)CD8(-)CD209a(+)) and human (CD1c(+)CD19(-)) myeloid dendritic cells (TIDC), an innate immune cell type also implicated in immune escape. However, there is little knowledge concerning how PD-1 regulates innate immune cells. In this study, we examined the role of PD-1 in TIDCs derived from mice bearing ovarian tumors. Similar to lymphocytes, TIDC expression of PD-1 was associated with expression of the adapter protein SHP-2, which signals to NF-?B; however, in contrast to its role in lymphocytes, we found that expression of PD-1 in TIDC tonically paralyzed NF-?B activation. Further mechanistic investigations showed that PD-1 blocked NF-?B-dependent cytokine release in a SHP-2-dependent manner. Conversely, inhibition of NF-?B-mediated antigen presentation by PD-1 occurred independently of SHP-2. Collectively, our findings revealed that PD-1 acts in a distinct manner in innate immune cells compared with adaptive immune cells, prompting further investigations of the signaling pathways controlled by this central mediator of immune escape in cancer. Cancer Res; 76(2); 239-50. ©2015 AACR.
Parent Project Number: 2P50CA136393-06A1 Sub-Project ID: 7026 Contact PI / Project Leader: KNUTSON, KEITH L
Title: PROJECT 8 - TH17 DENDRITIC CELL VACCINE Awardee Organization: MAYO CLINIC ROCHESTER
Contact PI / Project Leader Information: Program Official Information: Other PI Information: Profile Exists No Profile
Name: KNUTSON, KEITH L
Email: Click to view Contact PI / Project Leader email address
Title: PROFESSOR Name: Unavailable Not Applicable
Organization: Department/ Organization Type: Congressional District:
Name: MAYO CLINIC ROCHESTER
City: ROCHESTER Country: UNITED STATES (US) Unavailable
Other Domestic Non-Profits State Code: MN
District: 01
Other Information:
FOA: PAR-14-031
Study Section: Special Emphasis Panel [ZCA1-RPRB-C (M1)]
Fiscal Year: 2015 Award Notice Date: 24-SEP-2015 DUNS Number: 006471700
Project Start Date: 1-OCT-2008
Budget Start Date: 11-SEP-2015 CFDA Code:
Project End Date: 31-AUG-2020
Budget End Date: 31-AUG-2016
Administering Institutes or Centers:
NATIONAL CANCER INSTITUTE
Project Funding Information for 2015:
Total Funding: $265,812
Direct Costs: $265,812
Year Funding IC FY Total Cost by IC
2015 $265,812
Recent MRKR News
- Form 8-K - Current report • Edgar (US Regulatory) • 06/12/2024 08:05:47 PM
- Form SC 13D/A - General statement of acquisition of beneficial ownership: [Amend] • Edgar (US Regulatory) • 05/17/2024 10:25:14 PM
- Form 8-K - Current report • Edgar (US Regulatory) • 05/15/2024 08:40:16 PM
- Form 10-Q - Quarterly report [Sections 13 or 15(d)] • Edgar (US Regulatory) • 05/15/2024 08:03:21 PM
- Principal Investigator from City of Hope National Medical Center Invited to Present Clinical Data from Marker Therapeutics APOLLO Study at 11th Global Summit on Hematologic Malignancies • GlobeNewswire Inc. • 04/08/2024 11:00:39 AM
- Marker Therapeutics Reports Year-End 2023 Corporate and Financial Results • GlobeNewswire Inc. • 03/25/2024 09:45:00 PM
- Marker Therapeutics to Present at the H.C. Wainwright 2nd Annual Cell Therapy Virtual Conference • GlobeNewswire Inc. • 03/22/2024 04:30:51 PM
- Form 8-K - Current report • Edgar (US Regulatory) • 03/01/2024 01:02:47 PM
- Form 8-K - Current report • Edgar (US Regulatory) • 02/26/2024 12:58:51 PM
- Marker Therapeutics Receives Approval from United States Adopted Name (USAN) Council and International Nonproprietary Names (INN) Expert Committee for “Neldaleucel” as Nonproprietary Name for MT-601 • GlobeNewswire Inc. • 01/22/2024 12:30:00 PM
- Form 8-K - Current report • Edgar (US Regulatory) • 01/08/2024 01:30:48 PM
- Marker Therapeutics Announces Clinical Program Updates and Pipeline Prioritization • GlobeNewswire Inc. • 01/08/2024 01:24:49 PM
- Marker Therapeutics Announces Participation in Biotech Showcase and the 19th Annual Non-Dilutive Funding Summit During “J.P. Morgan Week 2024” • GlobeNewswire Inc. • 12/21/2023 04:00:00 PM
- Form 8-K - Current report • Edgar (US Regulatory) • 12/11/2023 12:35:22 PM
- Marker Therapeutics Announces Sustained Complete Response in First Lymphoma Patient Treated with MT-601 following CAR T Relapse • GlobeNewswire Inc. • 12/11/2023 12:00:00 PM
- Form 8-K - Current report • Edgar (US Regulatory) • 11/20/2023 09:37:41 PM
- Form 8-K - Current report • Edgar (US Regulatory) • 11/09/2023 10:03:53 PM
- Marker Therapeutics Reports Third Quarter 2023 Financial Results and Provides Business Updates • GlobeNewswire Inc. • 11/09/2023 10:00:00 PM
- Form 10-Q - Quarterly report [Sections 13 or 15(d)] • Edgar (US Regulatory) • 11/09/2023 09:31:53 PM
- Form 8-K - Current report • Edgar (US Regulatory) • 09/11/2023 11:10:46 AM
- Marker Therapeutics Announces Complete Response in First Lymphoma Patient Treated with MT-601 after CAR T Relapse • GlobeNewswire Inc. • 09/11/2023 11:00:00 AM
- Marker Therapeutics to Present at the H.C. Wainwright 25th Annual Global Investment Conference • GlobeNewswire Inc. • 08/30/2023 12:00:38 PM
- Form 8-K - Current report • Edgar (US Regulatory) • 08/14/2023 08:37:04 PM
- Marker Therapeutics Reports Second Quarter 2023 Financial Results and Provides Business Update • GlobeNewswire Inc. • 08/14/2023 08:30:27 PM
- Form 10-Q - Quarterly report [Sections 13 or 15(d)] • Edgar (US Regulatory) • 08/14/2023 08:03:55 PM
Mass Megawatts Announces $220,500 Debt Cancellation Agreement to Improve Financing and Sales of a New Product to be Announced on July 11 • MMMW • Jun 28, 2024 7:30 AM
VAYK Exited Caribbean Investments for $320,000 Profit • VAYK • Jun 27, 2024 9:00 AM
North Bay Resources Announces Successful Flotation Cell Test at Bishop Gold Mill, Inyo County, California • NBRI • Jun 27, 2024 9:00 AM
Branded Legacy, Inc. and Hemp Emu Announce Strategic Partnership to Enhance CBD Product Manufacturing • BLEG • Jun 27, 2024 8:30 AM
POET Wins "Best Optical AI Solution" in 2024 AI Breakthrough Awards Program • POET • Jun 26, 2024 10:09 AM
HealthLynked Promotes Bill Crupi to Chief Operating Officer • HLYK • Jun 26, 2024 8:00 AM