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Publication-only abstracts (abstract number preceded by an "e"), published in conjunction with the 2019 ASCO Annual Meeting but not presented at the Meeting, can be found online only.

An umbrella for the cytokine storm: Enabling precision detection of CRS in CAR-T therapy.

Sub-category:
New Targets and New Technologies (IO)

Category:
Developmental Immunotherapy and Tumor Immunobiology

Meeting:
2019 ASCO Annual Meeting

Abstract No:
e14223

Citation:
J Clin Oncol 37, 2019 (suppl; abstr e14223)

Author(s): Qimin Quan; NanoMosaic LLC, Cambridge, MA

Abstract Disclosures

Abstract:

Background: Cytokine release syndrome (CRS), a systemic inflammatory response observed with monoclonal antibody drugs and adoptive T cell treatments, has become a major issue for CAR-T therapy. CRS can present as a mild reaction requiring minimally invasive supportive care up to a severe systemic response resulting in patient death. Monitoring this response during these therapeutic treatments is non-trivial due the wide range of biomarker concentrations, small sample volumes, and long assay times. Current analytical methods are unable to address these needs, limiting the precision of CAR-T therapy and effective management of its side effects. Methods: Emerging studies in this area have focused in establishing a panel of predictive biomarkers to manage dosing and early interventions, among them, IFNγ, IL6, TNFα, MIP1 have shown predicative powers in pediatric patients. Nevertheless, a significant improvement (100x) on the detection sensitivity is required to predict the CRS response with currently available methods. In addition, CRS-associated biomarkers including CRP and ferritin vary from 10ng/mL-10mg/mL while other predictive biomarkers (eg, IL6, IFNγ, etc.) vary from 1pg/mL-100ng/mL. At present, no analytical tool, known to us, can provide this large dynamic range ( > 9 logs), with the requisite lower limit of detection, in a rapid single test to predict and differentiate low, medium or high grade responses. Results: We present the NanoMosaic platform, the technology that has requisite sensitivity and breadth of dynamic range to enable precision detection based on precise quantitation of CRS-relevant biomarkers. NanoMosaic technology is enabled by single molecule nanoneedle sensors that are densely integrated on a silicon chip and manufactured with a CMOS-compatible process. Absolute quantitation is achieved by imaging the spectrum of nanoneedles, corresponding directly to the number of molecules. Conclusions: Direct comparison of different protein biomarkers with orders of magnitude concentration variations becomes possible in one platform and small sample sizes. We envision NanoMosaic technology will not only drive biomarker discovery, but also enable precise dosing management for CAR-T therapy.

 
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1. A phase II, randomized, double-blind, placebo-controlled trial evaluating efficacy and safety of namodenoson (CF102), an A3 adenosine receptor agonist (A3AR), as a second-line treatment in patients with Child-Pugh B (CPB) advanced hepatocellular carcinoma (HCC).

Meeting: 2019 ASCO Annual Meeting Abstract No: 2503 First Author: Salomon M. Stemmer
Category: Developmental Immunotherapy and Tumor Immunobiology - New Targets and New Technologies (IO)

 

2. Results from a first-in-man, open label, safety and tolerability trial of CAN04 (nidanilimab), a fully humanized monoclonal antibody against the novel antitumor target, IL1RAP, in patients with solid tumor malignancies.

Meeting: 2019 ASCO Annual Meeting Abstract No: 2504 First Author: Ahmad Awada
Category: Developmental Immunotherapy and Tumor Immunobiology - New Targets and New Technologies (IO)

 

3. Determination of the recommended phase II dose of birinapant in combination with pembrolizumab: Results from the dose-escalation phase of BPT-201.

Meeting: 2019 ASCO Annual Meeting Abstract No: 2506 First Author: Russell J. Schilder
Category: Developmental Immunotherapy and Tumor Immunobiology - New Targets and New Technologies (IO)

 

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