Lichtenfeld: Sometimes the tech gets ahead of the application. Getting to a point with ctDNA as early det; will we know what to do? #NGDx17

11:51am August 16th 2017 via Hootsuite

Plenary session at #NGDx17 on D.C. policy and prediction for diagnostics https://t.co/tYjHV8R83u

11:51am August 16th 2017 via Hootsuite

Bennett: Now a separate line on the cost sheet for PAMA. Overheads are different. Can you imagine what it is for conjoined twin? #NGDx17

11:48am August 16th 2017 via Hootsuite

Fish: AdvaMedDx developed a value-based framework, how to explain value to different stakeholders, and what the value case is #NGDx17

11:45am August 16th 2017 via Hootsuite

Fish: Reimbursement - for manufacturers, what evidence is needed. Demonstration of value to their customers, whoever they may be #NGDx17

11:44am August 16th 2017 via Hootsuite

Fish: Long advocated for unified treatment of tests based on risk. Engaged w/ongoing debate of regulation. #NGDx17

11:42am August 16th 2017 via Hootsuite

Fish: May not all agree but all have the same goals. Envision a full leverage of Dx tests to improve public health. Regulation/reimb #NGDx17

11:41am August 16th 2017 via Hootsuite

Khani: Sees opportunity for LDTs to come to market with a strengthened CLIA for review by FDA #NGDx17

11:41am August 16th 2017 via Hootsuite

#NGDX17 con't Panelists Andrew Fish AdvaMedDx Michael Bennett (U Penn/CHOP) Leonard Lichtenfeld (ACS)

11:38am August 16th 2017 via Hootsuite

#NGDx17 Washington Insight: policy & prediction for Diagnostics. Bruce Quinn, Alberto Gutierrez (FDA) Mary Williams (AMP) Julie Khani (A

11:37am August 16th 2017 via Hootsuite

Qa; Why rh-based blocking only now? Jarosz: Why IDT opened up a San Francisco office, to develop tech they've had a long time #NGDx17

10:22am August 16th 2017 via Hootsuite

Q:'Barcode hopping has been driving us nuts' b/c of seq error Jarosz: Designed to e 2-3 errors apart, but at <1%, is all relevant #NGDx17

10:21am August 16th 2017 via Hootsuite

Jarosz: Have an rhAmp allele-specific PCR for SNP genotyping. Showed data w/collaborator for IDH1/2, implemented as an LDT at MGH #NGDx17

10:19am August 16th 2017 via Hootsuite

Jarosz: Took an add'l 49 commercial tumor tissue/plasma/normal tissue triads. A full 10% had not correct genotypes (!) #NGDx17

10:16am August 16th 2017 via Hootsuite

Jarosz: AstraZeneca (AZ) used 15 matched FFPE/plasma. 20% didn't have matching SNPs (!) #NGDx17

10:16am August 16th 2017 via Hootsuite

Jarosz: rhPCR - IDT has blocked the 3 end, with unique DNA:RNA hybrid primers. 3' blocker allows specificity compared to std primers #NGDx17

10:14am August 16th 2017 via Hootsuite

Jarosz: Sample mixups can (and do) occur, refers to NY piece https://t.co/Wma2W1Edky #NGDx17

10:13am August 16th 2017 via Hootsuite

Jarosz: IDT is partnering with Illumina on implementing this quickly, getting scale on many barcodes for the NovaSeq capacity #NGDx17

10:11am August 16th 2017 via Hootsuite

Jarosz: IDT worked on unique dual-indices, reducing cross-talk a '3-in-1' design. P5, i5 Index, insert, i7 index, UMI, P7 #NGDx17

10:10am August 16th 2017 via Hootsuite

Jarosz: Points to Sinha bioArXiv https://t.co/OLEJHRBLaO and Illumina's response #NGDx17

10:07am August 16th 2017 via Hootsuite

Jarosz: Shows 1- to 16-plex index hopping, on the order of 0.03%. Impt w/low frequency variation. #NGDx17

10:06am August 16th 2017 via Hootsuite

Jarosz: If two adjacent smpls share one of the two indexes, get index misassignment. Index hopping when samples mulitplexed w/cap #NGDx17

10:05am August 16th 2017 via Hootsuite

Jarosz: Introduces NGS workflow, and goes onto sample crosstalk problems, and dual indexing strategy available from Illumina w/20 #NGDx17

10:04am August 16th 2017 via Hootsuite

Mirna Jarosz (IDT) Nucleic acid technologies to enable clinical diagnostics - sample integrity to multiplex PCR #NGDx17

10:03am August 16th 2017 via Hootsuite

Epstein: Induce PBMC population w/tumor cells co-culture, isolate MDSC w/anti-CD33. Dev a suppression assay w/flow cytometry readout #NGDx17

9:10am August 16th 2017 via Hootsuite

Epstein: Also GM-CSF PGE2 IL-1b. Tumor cells produce these factors to inhibit MDSC. Shows BALB/c mouse data #NGDx17

9:07am August 16th 2017 via Hootsuite

Epstein: Function of MDSC is to prevent autoimmunity and modulate end-responses. MDSC factors ID'd from tumor cells IL6 TGFb VEGF #NGDx17

9:06am August 16th 2017 via Hootsuite

Epstein: Myeloid-derived suppressor cells (MDSC) are induced by the tumor by a number of cytokines, and closely associated w/Treg #NGDx17

9:03am August 16th 2017 via Hootsuite

Epstein: In about 50% of cancers are HLA negative. Their hypothesis - diverse mechanisms (immune evasion, direct supp, indirect) #NGDx17

9:00am August 16th 2017 via Hootsuite

Epstein: Cancer a balance between active tumor regression, and suppressed response that allows tumor growth. #NGDx17

8:57am August 16th 2017 via Hootsuite

Epstein: Recurrent and metastatic disease is the greatest mobidity, mortality. There are critical window for improving outcomes #NGDx17

8:56am August 16th 2017 via Hootsuite

Epstein: NeoAg can be given back, but you have to deal with suppression. Rare pop'ln of cells, <1% in normal. #NGDx17

8:55am August 16th 2017 via Hootsuite

Alan Epstein (Univ So Calif) The MDSC clinical assay for the immunodiagnosis and monitoring of solid tumors #NGDx17

8:54am August 16th 2017 via Hootsuite

Q: In silico validity? Mandal: Not very good right now (well, 'still') need to acknowledge and improve #NGDx17

8:53am August 16th 2017 via Hootsuite

Q: Min number of muts? Mandal: Not just the number, it's the quality. If 1 mut is immunogenic, that's all you need #NGDx17

8:52am August 16th 2017 via Hootsuite

Q: Company that does co-culturing? Mandal: Genocea More info on ID of specific, individual T-cell antigens https://t.co/zYZl29Hx1F #NGDx17

8:51am August 16th 2017 via Hootsuite

Mandal: #NGDx17 FInishes with a figure from a '16 review https://t.co/n6K7vxkFNZ on how the future of I-O may play out.

8:49am August 16th 2017 via Hootsuite

Mandal: Suggests a neoAg pipeline: PMBCs, take autologous dendtritic cells, co-culture to ID the antigen. #NGDx17

8:47am August 16th 2017 via Hootsuite

Mandal: WES and RNASeq give T-cell repertoire, eval clonality, look at neoAg, Class I/II processing. #NGDx17

8:45am August 16th 2017 via Hootsuite

Mandal: #NGDx17 '16 JCI Insight https://t.co/lKGMLmACvF Head and Neck - shows high NK cell infiltration; correlated to positive outcome

8:44am August 16th 2017 via Hootsuite

Mandal: Shows clonality in these tumors. Also defectsin Ag presentatio can cause immune escape, incl defects in methylation #NGDx17

8:43am August 16th 2017 via Hootsuite

Mandal: MMR deficiency across cancers '15 Nature Med https://t.co/vg3qFkijJI #NGDx17

8:41am August 16th 2017 via Hootsuite

Mandal: #NGDx17 '15 NEJM https://t.co/vd9w1Tb1Md shows MMR deficiency. MMR causes slippage, MSH2/6/MLH1/PMS2. Any one impairs repair

8:41am August 16th 2017 via Hootsuite

Mandal: Shows fig from Rizvi '15 of distribution of DNA repair genes in NSCLC responders to Pembro #NGDx17

8:39am August 16th 2017 via Hootsuite

Mandal: In NSCLC, shows mutational burden w/Pembro '15 Science https://t.co/lNYrslYgX7 #NGDx17

8:38am August 16th 2017 via Hootsuite

Mandal: Snyder NEJM '14 shows mut load correlates with clinical benefit in melanoma / ipi https://t.co/7rzvg7XnPH #NGDx17

8:37am August 16th 2017 via Hootsuite

Mandal: Shows neoAg by MHC to CD8+ cells. Fig from Chen and Mellman '13 Cancer-Immune cycle and promotion of anti-tumor activity #NGDx17

8:36am August 16th 2017 via Hootsuite

Mandal: Shows type of neo-Ag. Type I, II is invisible, mutation causes HLA presentation. III is frameshift casting novel peptide #NGDx17

8:35am August 16th 2017 via Hootsuite

Mandal: I-O is a fire extinguisher. Shows Ferris NEJM 2016 https://t.co/yWtpnHnWyi figure on poor prognosis of PD1/L1 as biomarker #NGDx17

8:34am August 16th 2017 via Hootsuite

Mandal: If cancer is a fire, there may be different types of fuel: p53, RAS, BRAF, PIK3, EGFR. Targeted Rx = other fuel sources #NGDx17

8:31am August 16th 2017 via Hootsuite