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Expert Interview

Slingshot members are talking to an expert! The topic is:

SPONSORED BY LONCAR INDEX - Third Annual Key Takeaways in CAR-T from ASH 2017


Who's the expert?

Name: Dr Stephan Grupp - MD/ PhD

Institution: University of Pennsylvania


  • Director of the Cancer Immunotherapy Frontier Program, director of Translational Research for the Center for Childhood Cancer Research and medical director of the Stem Cell Laboratory
  • Has led a group that performed a nationwide clinical trial establishing antibody-based immunotherapy as the new standard for care in neuroblastoma.
  • Has received several awards throughout his career and is a member of a number of professional organizations including the International Society for Cell Therapy, American Pediatric Society, American Society of Hematology, American Society of Blood and Marrow Transplantation and more

Interview Questions

Good to speak with you again, for those who aren't familiar with your work could you tell us a bit about your current research focus and patients you care for?

Added By: joe_mccann

What was the overall sentiment at ASH this year, particularly in light of the first approvals in CAR-T?

Added By: joe_mccann

Where do "off-the-shelf" CAR-Ts stand after ASH this year? Which programs are most interesting on this front and do any have a mid-term path forward.

Added By: joe_mccann

Which new indications are most interesting for us to focus on in 2018? Are you hopeful for success in these?

Added By: joe_mccann

With 2 approved therapies since we last spoke, what have you heard from your colleagues about the initial launch? GILD has indicated a hope for 80 hospitals to have access by the end of 2018, how does that compare to your expectations?

Added By: joe_mccann

How early (what line of therapy) do you feel CAR-Ts will have the opportunity to move into used in MM, DLBCL and AML in the future?

Added By: userda0312f6

We know that elevated levels of GM-CSF correlate with severe neurologic toxicities and preclinical studies suggest that GM-CSF and perforin are essential for CART related adverse events (even in an IL6 knockout mouse model).  Do you believe GM-CSF neutralization prior to CART cell therapy can potentially prevent neurologic toxicity? (Esp as tocilizumab currently appears to have no impact on NT).  Moreover, do you believe if neurologic toxicities and CRS can be prevented it will bring treatment closer to the patient, alleviating the requirement for treatment initiation at a transplant center and thus decreasing direct/indirect hospital costs?  

Added By: omara50

Cellectis has seen patient deaths related to CRS complications for both its allogeneic CAR Ts in the clinic, UCART19 and UCART123. Two deaths related to CRS when n = 12 treated is clearly not good. Is there any reason to believe allogeneic CARs should be inherently less safe than autologous, or do you see other problems (eg. with Cellectis' tech).

Added By: jjhedden

The AML pharma-pipeline is known as the “Pharma Graveyard” and “The boulevard of broken dreams”.
Given the mixed results of UCART123 how likely do you think it is that AML can successfully be treated by CAR-T therapies?

Added By: christopherfunk

Looking at Cellectis's UCART19 presentations in childhood and adult ALL, there were nice responses but plenty of early relapses. Can persistence be improved with higher dosing, or is there a fundamental problem with Cellectis's allogeneic concept?

Added By: jacobplieth

One new theme that emerged from ASH was the possibility of treating CAR-T subjects as outpatients (only in lymphoma for now, not childhood ALL). How compelling do you find this idea?

Added By: jacobplieth

Can you see any CAR-T developments that could replace allo Tx in AML?

Added By: christopherfunk

Last year you've  touched the solid tumors question as open with Adaptimmune TCR being a single successful example - have early positive TCR results from KITE (now Gilead) confirmed an advantage of TCR over CAR here or do you see CAR-T progress at the wall?

Added By: dhovekamp42

Do you think 5T4 (expressed on many solid tumours) would be a good antigen  target for solid tumours and perhaps better if combined with other targets and a PD-1? Oxford Biomedica supply the Lenti for CTL019 and have moved to larger bio-reactors. Can you see further improvements happening? Congratulations on your fantastic work. You should be very proud, thank you.

Added By: user4822b6e5

How compelling did you find Juno's SITC presentation on the possible causes of cerebral oedema in the JCAR015 study? What are the key things we have learned from this analysis?

Added By: jacobplieth

Do you think that CAR-T therapies can replace allo Tx in B-ALL any time soon?

Added By: christopherfunk

Can Bluebird's bb2121 BCMA data in multiple myeloma be beaten?

Added By: jacobplieth

Also Affimed has T-cell engagers (AFM11 CD19/CD3 in clinical trials for NHL and ALL) the presented AFM13/AFM26 are directed at NK-cells for which cell-based CAR where also presented at ASH (e.g. Fate Therapeutics  or Affimed partner MDAnderson ).  
One advantage of NK-Cells is said to be their 'off-the-shelf' use is easier to archive.

How do you see such CAR-NK cell therapy versus CAR-T?

Added By: dhovekamp42

How do you view the lymphoma data, as updated at ASH, from Juliet (Kymriah), Zuma-1 (Yescarta) and Transcend-NHL (JCAR017)? Are they basicaly showing the same thing? Does any dataset look better than the others?

Added By: jacobplieth

Has Juno's surprising desire to push into engineered TCRs changed your opinion of the potential of these therapeutics versus CARs?

Added By: jacobplieth

What is your view of the potential of CD22-directed CAR-T, given the updates presented at ASH?

Added By: jacobplieth

Do you think think the idea of treating CAR-T subjects as outpatients (proposed by Novartis in Juliet and Juno in Transcend-NHL) is driven primarily by a desire for patient welfare or a desire to save on hospital costs?

Added By: jacobplieth

After the downfall of Juno's Rocket trial, Gilead's Zuma-3 is the only active, company-sponsored study of CAR-T in adult ALL. What is your view of this indication?

Added By: jacobplieth

Do you have any thoughts about Actinium Pharmaceuticals' Positive Preliminary Results from Phase 2 Trial for Actimab-A? Or their Actinium-225 Labeled Daratumumab data at ASH? 

Added By: philk

There is a notion of 'CAR in a vial' for constructs like Amgen's Blincyto BiTE (Bispecific T-cell Engager) that allow immune cells to find and destroy cancer cells without extracting and gene-manipulating patient's blood.

Example given: this year at ASH Affimed has released first safety and preliminary efficacy data of its AFM13 CD30/CD16a NK-cell engager in combination with Merck Anti-PD1 Keytruda in R/R Hodgkin Lymphoma (see ). ORR was >80% at the target dose (a cohort of 6/12 with 4 infusions at 3 month by independent assessment reached 5 PR, 1 SD, One of the PmR was assessed CmR after another 4 infusions at 6 month treatment. The 6 patients at lower dosis also already showed 1 CR and 4 PR at 3 month).

Affimed also showcased a preclinical BCMA targeting immune-cell engager AFM26 (see ) that would compete with the 'Star of ASH' bb2121 (21 patients with ORR 86% and CR 56% at 9 month) from bluebird Bio / Celgene and other CAR-T (see ).

Where would you see this kind of approach versus classical cell -based CAR-T?

Added By: dhovekamp42

Did you see any noteworthy progress being made by CARs using humanised or fully human binders at ASH? eg, CTL119.

Added By: jacobplieth

Do you think any oncologist would select a CAR-T therapy that wasn't best in class? Why would any patient/Dr. want any CAR-T therapy that didn't give the highest success rate for remission and the lowest side effect profile regardless of price and even if the differences among various CAR-T company success rates are minimal. In other words, why would anyone choose Kite/Gilead or Novartis over Juno? I could understand choosing a slightly inferior intervention if we were dealing with hypertension but for oncology ...

Added By: jjmcnasty

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