Immunotherapeutic targeting of MIF-dependent chaperone activity

Active Project Grant Awarded Last action

Award ID
R01CA279748
Recipient
Awarding agency
Obligated
$3,054,649

Award facts

Assistance listing
93.395 Cancer Treatment Research
Completion date 71% complete
Place of performance
Louisville, KY 40202, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
"immunotherapeutic targeting of MIF-dependent chaperone activity" metabolic reprogramming that favors mitochondrial respiration plays an important role in controlling differential gene expression patterns in myeloid lineage cells. Our recent findings have identified a novel protein chaperone-dependent pathway that indirectly controls mitochondrial homeostasis and metabolic programming that are needed to drive maximal intratumoral myeloid cell immune suppressive phenotypes. Our hypothesis predicts that small molecule inhibition of this chaperone activity, carried out by the multifunctional cytokine MIF, induces spontaneous CU/ZN superoxide dismutase (SOD1) misfolding and aberrant mitochondrial binding leading to metabolic reprogramming and subsequent phenotypic reversion of intratumoral myeloid cell immune suppressive phenotypes into immune stimulatory phenotypes. Studies proposed in this application will: 1) delineate the mechanisms of action of 4-IPP-based MIF chaperone inhibitors in the context of MIF/SOD1- dependent TAM/mdsc polarization; 2) determine the relative contribution of hypoxia as a physiologic ER stressor that exacerbates myeloid WT SOD1 misfolding in the context of MIF and 4-IPP, and 3) evaluate the therapeutic potential of lead MIF chaperone antagonists as individual and combinatorial modalities against established metastatic melanoma.

Transactions

Action Obligated Date
Amendment $342,990
Amendment $34,179
Amendment $34,179
Amendment $307,603
Amendment $307,603
Amendment $17,152
Amendment $17,152
Amendment $308,690
Amendment $308,690
Amendment $308,690
Amendment $355,907
Amendment $355,907
Original award $355,907
Show all 13

Subawards

Subrecipient Amount Awarded
Ben Gurion University Of The Negev This subcontract is between the laboratory of Dr. Robert A. Mitchell at the University of Louisville and the laboratory of Dr. Adrian Israelson at the Ben… $36,118
Ben Gurion University Of The Negev Amendment #2. New funds awarded. No change to the current SOW in place $40,969

Quick answers

Who received award R01CA279748?

R01CA279748 was awarded to University Of Louisville by National Cancer Institute (National Institutes of Health) on April 1, 2023.

How much is award R01CA279748 worth?

$3,054,649 has been obligated on R01CA279748.

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