Stam.: (abbrev. for Stamatoyannopoulos): The normal state: hESCs move down the 'valleys'. Can det which TF's involved ea step #AACR14
1:46pm April 7th 2014 via Hootsuite
Stamatoyannopoulos: DHS gains/losses highlight key regulatory factors; Ref 2013 Cell Stergachis et al http://t.co/Fe701Vbhhf #AACR14
1:44pm April 7th 2014 via Hootsuite
Stamatoyannopoulos: hESC w/ 257K DHSs, Hematopoeitc progenitors, gain 83K, lose 202K DHSs. ~40% of hESC DHSs' preserved #AACR14
1:42pm April 7th 2014 via Hootsuite
Stamatoyannopoulos: PCoA of DNAseI hypersensitivity (3D plot) - orbiting around hESC's #AACR14
1:41pm April 7th 2014 via Hootsuite
Stamatoyannopoulos: Extensive memory (chromatin, TF's) preserved in terminally differentiated cells #AACR14
1:40pm April 7th 2014 via Hootsuite
Stamatoyannopoulos: hESC's sit at the top - derivatives of primitive mesoderm. 'Lineage memory' encoded in cellular reg DNA #AACR14
Stamatoyannopoulos: Introducing the epigenetic landscape via ENCODE project http://t.co/sNzMQfeWoT #AACR14
1:38pm April 7th 2014 via Hootsuite
Up first: John Stamatoyannopoulos, Univ Washington: "Reactivationn of early developmental programs during oncogenesis" #AACR14
1:37pm April 7th 2014 via Hootsuite
Symposium: "Functional regulation of the cancer genome". Chair: Brad Bernstein, Broad Institute. #AACR14
Rosenberg: Determined that 26.9% of the TIL's from an individual tumor were specific to the tumor mutated antigen #AACR14
12:44pm April 7th 2014 via Hootsuite
Rosenberg: Now looking at TCR clonotypes that recognize individual's mutations. Most abundant (fresh tumor) is spec to that cancer #AACR14
12:42pm April 7th 2014 via Hootsuite
Rosenberg: ID ERBB2IP gene (the single antigen), used for adoptive therapy. The 'ultimate "personalized therapy" ' In ~6 wk time #AACR14
12:38pm April 7th 2014 via Hootsuite
Rosenberg: WES of lung metastasis - found 26 nsSNVs, did tandem minigenes of all 26, only 1 / 3 TMG, identified single antigen #AACR14
12:36pm April 7th 2014 via Hootsuite
Rosenberg: Now with 25 samples; each with a unique mutation. #AACR14
12:35pm April 7th 2014 via Hootsuite
Rosenberg: Constructing a tandem minigene - to express all the mutated peptides, all tested against TIL of complete regress'n #AACR14
12:33pm April 7th 2014 via Hootsuite
Rosenberg: Illustrates examples of very low-likelihood binders that have been shown to be the spec peptide antigen #AACR14
12:32pm April 7th 2014 via Hootsuite
Rosenberg: Then screen for invitro recognition by TIL cells that mediate complete regression #AACR14
12:29pm April 7th 2014 via Hootsuite
Rosenberg: For a mut to be a cancer antigen - 9- or 10-mer peptide ID'd, synthesize 20-40 candidate peptides with high MHC affinity #AACR14
Rosenberg: The puzzle of melanoma immunogenicity - unique in susceptibility to cytokins. From WES, looking at wide # of nsSNV #AACR14
12:28pm April 7th 2014 via Hootsuite
Rosenberg: Success rates are irrespective of prior melanoma treatment regimen #AACR14
12:26pm April 7th 2014 via Hootsuite
Rosenberg: "TIL appear to eliminate the last cancer cell' with such long time-frame of complete regressions #AACR14
Rosenberg: Photo of a nasty melanoma: 8y on now disease-free; only one to require 2nd treatment #AACR14
12:25pm April 7th 2014 via Hootsuite
Rosenberg: 8.8y followup: Of 93, 22% have a complete response, 19/20 CRs ongoing at 80-120 months #AACR14
12:23pm April 7th 2014 via Hootsuite
Rosenberg: From decades ago: adoptive transfer of TIL - tumor removed, IL-2 stim, select, expand, administer #AACR14
12:22pm April 7th 2014 via Hootsuite
Rosenberg: To use lymphocytes for treatment. Chart of advantages: large #'s, activated ex-vivo, ID cell subpops, can manipulate host #AACR14
12:21pm April 7th 2014 via Hootsuite
Next: Steven Rosenberg, Chief of Surgery, NCI. "The curative potential of T cell transfer therapy for patients with cancer" #AACR14
12:19pm April 7th 2014 via Hootsuite
Weissman: 5F9g4 humanized Ab is headed to AML trial. $20M CIRM grant for 'an all comers solid tumor' trial #AACR14
12:16pm April 7th 2014 via Hootsuite
Weissman: Targeting CD47 "Every human cancer we see has CD47'. Can get statis but not removal. #AACR14
12:13pm April 7th 2014 via Hootsuite
Weissman: Young cells ++exp CD47 to evade phagocytosis; 'in 3 mos the smartest (new) person becomes the stupidest' thinking alike! #AACR14
12:04pm April 7th 2014 via Hootsuite
Weissman: If prog. in HSC clone for AML is true, 'it is probably true for all cancers' in tissues that regen. from tiss. stem cells #AACR14
12:01pm April 7th 2014 via Hootsuite
Weissman: Looking at NGS exomes to ID somatic mut's in AML. List of ~25 genes; determined order of mutations. Single HSC analysis #AACR14
12:00pm April 7th 2014 via Hootsuite
Weissman: Looking at GSK3-beta expression by blast crisis CML progenitors. But for epigenetics need specific subsets #AACR14
11:58am April 7th 2014 via Hootsuite
RT @00livier: Weissman: no overlap of interest between academia and industry in stem cell therapy #AACR14
11:55am April 7th 2014 via Hootsuite
Weissman: Figure of hematopoeitc pathway. Ref Miyamoto 2000 PNAS ref http://t.co/ifX4HibY1l #AACR14
11:54am April 7th 2014 via Hootsuite
Weissman: Cancer-free stem-cell grafts improves survival - fig. from 2011 Muller et al ref: http://t.co/Au2ciR7vkf #AACR14
11:52am April 7th 2014 via Hootsuite
Weissman: Can remove contam. cancer and T-cell from stem cell grafts #AACR14
11:49am April 7th 2014 via Hootsuite
Next: I. Weissman Stanford. "Investigating inhibition of the CD47 'don't eat me' signal to enable tumor phagocytic removal..." #AACR14
11:48am April 7th 2014 via Hootsuite
June: Key issues: Dose / freq; B cell aplasia; CAR design for persistence; role in therapy for ALL; CD19 escape freq (~5% observed) #AACR14
11:46am April 7th 2014 via Hootsuite
June: Six institutes developing many targets, 4 int'l institutes also for CART19, and several pharmas #AACR14
11:45am April 7th 2014 via Hootsuite
June: How to scale to 1000's? Automation of robotic and cell culture. Mag bead T-cell enrichment, cryopreserved, ongoing work #AACR14
11:43am April 7th 2014 via Hootsuite
June: Toxicities include B-cell aplasia, Tumor Lysis syndrome, Cytokine release syndrome #AACR14
11:42am April 7th 2014 via Hootsuite
June: Roadblocks - have solved targeting, expansion; however toxicity is being addressed #AACR14
11:40am April 7th 2014 via Hootsuite
June: 7/16 adults in complete remission for ALL. Listed 6 potential roles for CAR Tcells for ALL, including an 'allo-Stem Cell XP' #AACR14
11:38am April 7th 2014 via Hootsuite
June: CARs shown to still persist 6mo. Have tracked to cerebral-spinal fluid. Rationale for neuro-oncology. #AACR14
11:37am April 7th 2014 via Hootsuite
June: Grupp speaking Tues 10:30am in pediatric session. #AACR14
11:34am April 7th 2014 via Hootsuite
June: Shift to ALL, Leukemial is still #1 pediatric cancer mortality, new treatment needed. Using CART19, Grupp 2013 NEJM ref #AACR14
11:33am April 7th 2014 via Hootsuite
June: Using qPCR of peripheral CTL019 cell expansion, distinguishing responders (>6% mononuclear cells threshold) #AACR14
11:31am April 7th 2014 via Hootsuite
June: Sustained Ab delivery with a single infusion of engineered T-cells shown. Showed expansion, persistence of CAR19+ cells #AACR14
11:30am April 7th 2014 via Hootsuite
June: Showed responsiveness and figures from David Porter, UPenn 2013 NEJM paper: http://t.co/60NFZcOVU1 #AACR14
11:29am April 7th 2014 via Hootsuite
June: Context of CLL survival: autologous T-cells, frozen. NCT01029366 NEJM ref 2013 http://t.co/n3AAZjG2Ch #AACR14
11:27am April 7th 2014 via Hootsuite
