Immunotherapies and Mechanisms of Immune Escape

Forum Chairs

Esra
Akbay
,
PhD
Dana-Farber Cancer Institute
Monica
Guzman
,
PhD
Cornell Medical College

Forum Description

Modern immunotherapy concepts have changed cancer treatment paradigms, such as immune checkpoint blockade, chimeric antigen receptor (CAR) T cells, and antibody-based therapies have made rapid progress in the past 10 years and are currently used to treat many cancers. Immune checkpoint inhibition circumvents tumor-induced suppression of cytotoxic T cell function. Adoptive transfer of T cells expressing chimeric antigen receptors (CARs) are currently approved treat CD19-positive cancers. However, only a fraction of patients responds, especially in the field of solid tumors as, for example, the immune microenvironment plays a critical role in disease progression and outcomes as it can induce immune suppressive signals that prevent immune-surveillance and allow malignant cells to persist. Therefore, combination treatments using different kind of immunotherapies targeting multiple checkpoints are necessary for more effective responses. Discussing all the components that are known to play a role in the mechanisms of immune escape and the emerging concepts for therapeutic interventions in a multidisciplinary setting will lead to the implementation of rationally designed trials to better harness immune system for the benefit of cancer patients.

Forum Summary

The forum was set to discuss the role of the tumor microenvironment in preventing immunotherapies from eliminating tumors. Novel concepts such as bioengineering models, delivery systems, the genetic and epigenetic make up, identification of new targets, and combinatorial therapies were also discussed. The participants were from diverse disciplines which allowed for cross fertilization of ideas and will likely result in new innovative collaborations.

The Forum was divided into 4 sections, structured to (1) discuss challenges that have hampered the success of antigen receptor (CAR) T targets and immune checkpoint inhibitors in solid and liquid tumors; (2) present innovative technologies that can help overcome some challenges evaluating or implementing immune therapies; (3) evaluate the components of the tumor microenvironment or other factors that may contribute to resistance to immune therapies; (4) propose alternative therapeutic approaches to improve upon immune therapies.

Briefly, Fabiana Perna talked about challenges when selecting chimeric antigen receptor (CAR) T targets as often may have toxicity against normal tissues, she discussed a novel platform for the discovery of novel CART targets using unbiased proteomic approaches. Andrei Thomas-Tikhonenko covered the mechanism that result in escape of tumors cells to CAR T cells in leukemia which involve splicing changes that result in the lack of the expression of the antigen on the cell surface of the cells. Such changes also affect response to antibody drug conjugate therapies by the loss of antibody target antigens through splicing alterations.

Esra Akbay talked about the relevance of tumor mutational burden (TMB) as a biomarker for sensitivity checkpoint blockade therapy and potential implementation of novel mouse models and their limitations.

Ankur Singh presented innovative hydrogel models and bioreactors to evaluate 3D structures such as tumor organoids. This opened an interest for the potential integration of immune cells into these systems to mimic the tumor microenvironment to better understand and address mechanisms of resistance. Jinming Gao talked about the nanotechnology tools to examine pH in tumors in vivo models and human clinical trials. This approach allows for improved visualization of the tumors for resection. Furthermore, he discussed nanoparticle encapsulated cancer vaccine potentiating STING pathway (a key mediator of inflammation) locally. Michael Birnbaum presented his high throughput screen approach to test all potential combinations signaling domains to improve upon activity of CAR T cells.

David Raulet talked about stimulating NK cells by cyclic dinucleotides activating molecules to target CD8 T cell resistant tumors some of which lack antigens or do not present antigens. He also described a superkine IL2 approach that can overcome NK cell exhaustion. David DeNardo talked about how different tumor microenvironments (lung vs pancreas) have different immune context and different response to ICB. He showed that this was due to dendritic cell absence in pancreas. Lucy Godley lead a discussion around the impact of germline mutations that may affect the tumor microenvironment, in addition to pre-disposing events such as clonal hematopoiesis that also may impact the response of patients to immune therapies.

Lorenzo Galluzzi discussed a combinatorial approach of radiation therapy to improve CAR T cell therapies via a CAR independent interaction. Monica Guzman discussed the role of epichaperome inhibitors as a mechanism to improve immune responses in patients. Stephanie Dougan, dynamically presented how T cells can mediate resistance to immune checkpoint inhibitors.

Overall, all discussions were very dynamic and interactive. Several collaborations we discussed to for example: Improve delivery of inhibitors via nanoparticles, to implement novel bio engineered models to study the role of immune cells in tumor organoids, to anticipate mechanism of resistance in novel discovered CAR T targets evaluating splicing events.

Venue & Travel Information

Hilton Denver Inverness

200 Inverness Drive West
Englewood, CO 80112

hilton.com
303-799-5800

Travel Forms

Travel forms are due 30 days prior to the start of the meeting to allow enough time to plan transportation.

Denver International Airport (DIA) is approximately 30 minutes from the meeting location.

  • Arrivals - Thursday around 1 PM, 3 PM and 5 PM
  • Departures - Sunday around 10 AM and 12 PM
TRAVEL FORMS DUE:
September 28, 2021
submit travel form

Travel Policy

Please familiarize yourself with our policies and procedures for travel. We truly appreciate you taking the time to participate in this meeting. As you make your plans, please remember that we are a nonprofit organization dependent on donations and volunteers. We do NOT pay for upgrades, change fees, incurred costs resulting from a flight change, transportation to or from your local (home side) airport, meals or other incidentals.

  • Travel Confirmation will be sent out within 1 week of the meeting. This will include a hotel confirmation number, if there is one, and airport transfer details. We have to wait until we receive almost everyone’s travel to book airport transfer. Due to frequent airline changes, we wait until the week of the meeting to send this out.
  • Airport transfer is provided by Foundation staff, volunteers or arranged shuttle at specific times. If you opt to utilize Foundation airport transportation on your travel form, please be patient in receiving this information. We will send it to the week of the meeting.
  • Speaker agenda is not sent out prior to the meeting. It will be provided upon arrival in the meeting packet. We do not tell people when they are speaking because we expect everyone to attend all sessions. Sessions are all day Friday and Saturday.
  • REMINDER: We do not reimburse for home side airport transfer or incidentals while traveling. We will not honor miscellaneous receipts sent for these expenses.
  • Spouses are welcome to come with you at their own cost but are not allowed to attend the meeting. Please no children.

What the Foundation Pays

Accommodations and meals are provided by the foundation during the meeting. Airfare will be covered only if booked through our travel agent. The Foundation will also cover airport transportation on the meeting side at the designated shuttle times. You can select not to utilize Foundation arranged transportation at your own expense when completing the travel form. Once your travel form is received your accommodations and airport transfer will be confirmed. Please let us know of any food allergies or other information we should be aware of on the travel forms.

  • If you would like your airfare covered by the Foundation, you must book with our travel agent. Note we do not cover upgrades, changes, late bookings, etc.
  • Flights must be booked at least 30 days prior to the meeting to confirm your accommodations and airport transfer.
  • As a nonprofit we utilize volunteers and other methods to maximize our efforts (or our donor support) when making accommodations and arranging ground transportation. Ground transportation will be provided upon your arrival either by a foundation volunteer or arranged shuttle. You will be provided airport transportation information the week of the meeting. We do not reimburse for home side airport transfer or incidentals while traveling.

Abstracts

Abstracts are due 30 days prior to the start of the meeting to allow enough time to prepare the meeting book.

The abstracts should be only one or two paragraphs outlining the theme of your presentation and should reflect the objective and spirit of the meeting (see above). Abstracts will be circulated about one week before the meeting. The meeting organizer will start requesting them a month before the meeting.

abstracts DUE:
September 28, 2021
submit abstract

Meeting Structure

The meeting structure has been developed over years of experience.

  • Participants have approximately 45 minutes, depending on the number of participants, for their presentation and discussion. The presentation is meant as a conversation start and should last about twenty minutes briefly covering background information and areas that are new or need further input. This should be structured in such a way as to lead to a lively discussion. Participants are encouraged to interrupt to ask questions or start discussions.
  • A MAXIMUM of 5 slide equivalents per presentation is allowed (Power point slides should not contain more than one graph or gel per slide and no more than 5 bullet points to stress the points being made by the presenter.) We appreciate cooperation with the spirit of this guideline. Handouts are welcome but should be distributed before sessions.
  • Everyone is expected to actively participate in every session and discussions.
  • The time spent at the meeting is relatively short, so please be familiar with papers received prior to the meeting.
  • It is very important that you commit to all sessions of the 2 days of meetings.

Forbeck Scholars Participation

Scholars are selected for each Forbeck Forum. These are outstanding junior clinical or post-doctoral fellows selected based on the quality and relevance of science.

  • Scholars present for 30-45 minutes, depending on the number of participants
  • The same presentation rules apply for scholars
  • After the Forum you are selected to attend, you will attend three years of Scholar Retreats held in Lake Geneva, WI. If you attend a Fall Forum, you will attend the Spring Retreat. If you attend a Spring Forum you will attend a Fall Retreat.
  • Scholars are selected by the Foundation Scientific Advisory Board and peer reviewers selected from past Forbeck Scholars.

General Program

The outline below illustrates a typical program schedule. You will receive a complete schedule, including speaking times, the Thursday the meeting starts.

Arrival Day
1:00 PM Arrivals
6:00 PM Cocktails (opt'l)
7:00 PM Dinner
Meeting Day 1
7:00 AM Breakfast
8:00 AM Scientific Sessions
12:00 PM Lunch
1:30 PM Scientific Sessions
6:00 PM Cocktails & Dinner
Meeting Day 2
7:00 AM Breakfast
8:00 AM Scientific Sessions
12:00 PM Lunch
1:30 PM Scientific Sessions
6:00 PM Cocktails & Dinner
Departure Day
7:00 AM Breakfast
8:00 AM Departures

Frequently Asked Questions

Below are some of our most Frequently Asked Questions. If you have something new to ask, please feel free to contact us.

  • Travel Confirmation will be sent out within 1 week of the meeting. This will include a hotel confirmation number, if there is one, and airport transfer details. We have to wait until we receive almost everyone’s travel to book airport transfer. Due to frequent airline changes, we wait until the week of the meeting to send this out.
  • Airport transfer is provided by Foundation staff, volunteers or arranged shuttle at specific times. If you opt to utilize Foundation airport transportation on your travel form, please be patient in receiving this information. We will send it to the week of the meeting.
  • Speaker agenda is not sent out prior to the meeting. It will be provided upon arrival in the meeting packet. We do not tell people when they are speaking because we expect everyone to attend all sessions. Sessions are all day Friday and Saturday.
  • Frequently airport transfer is provided by volunteers. Please be patient on receiving this information. Airport transfer will be sent out prior to arrival.
  • REMINDER: We do not reimburse for home side airport transfer or incidentals while traveling. We will not honor miscellaneous receipts sent for these expenses.

Forum Participants

Michael
Birnbaum
,
PhD
Massachusetts Institute of Technology
Greg
Delgoffe
,
PhD
University of Pittsburgh
David
DeNardo
,
PhD
Washington University
Stephanie K.
Dougan
,
PhD
Dana-Farber Cancer Institute
Lorenzo
Galluzzi
,
PhD
Weill Cornell Medical College
Jinming
Gao
,
PhD
UT Southwestern Medical School
Annette
Künkele
,
MD
Charite - University Hospital Berlin
Fabiana
Perna
,
MD PhD
Indiana University
David
Raulet
,
PhD
University of California Berkeley
Ankur
Singh
,
PhD
Georgia Institute of Technology
Andrei V.
Gudkov
,
PhD, DSci
Cleveland Clinic Foundation
Marcel
Van Den Brink
,
MD
Memorial Sloan Kettering Cancer Center
Alexandra-Chloe
Villani
,
PhD
Massachusetts General Hospital

Forum Scholars

Hyo Sik Jang, PhD
Van Andel Institute
Giulia Petroni, PhD
Weill Cornell Medical College