Gene Therapy & Tumor Vaccines

Drew
Pardoll
,
MD, PhD
Johns Hopkins University

Forum Description

Sessions:

  1. Immune Regulation
  2. Antigen Presentation and the Characterization of Tumor Specific Antigens
  3. Antigen-Based Vaccine Strategies
  4. The Transition from Animal Models to Clinical Protocols

The eighth Annual Forbeck Forum covered one of the most exciting new topics to emerge in cancer therapy. Basic immunologists as well as cancer immunologists and cancer gene therapists were brought together to develop new concepts in engineering the immune system to react against cancer antigens. It is now known that cancer cells, because of genetic changes that occur during the process of cancer development, contain a number of new proteins, both on their cell surface and inside their cells that distinguish them from the normal cells from which they arose. If it were possible to train the immune system to recognize these cancer antigens as something foreign and unwanted in the body then an individual’s own immune system could be used to turn against and attack their cancer cells.

In the past, immunotherapy strategies for cancer have involved the use of tumor vaccines that have shown some promise but not significant effectiveness. Over the last 5-10 years there has been a tremendous amount of information learned about the molecules that control immune responses. Furthermore, we now understand how one of the most potent cells in the immune system – the T cell – recognizes its antigen. Also, new techniques have been developed to efficiently transfer genes into cells, allowing scientists to molecularly engineer these cells to behave differently."

Forum Summary

In the initial scientific session of the meeting, John Yewdell described experiments to delineate how the cell produces pieces of antigens and combines them internally with molecules entitled MHC proteins that act as a molecular conveyor belt to bring these antigens to the surface of the cell. Once at the surface of the cell, they can be recognized by T cells. David Lo described animal models of autoimmune disease and discussed how the inappropriate immune responses, leveled against self- antigens that cause diabetes, teach us how one could potentially modify immune responses as therapeutic agents against cancer cells.

In the second scientific session, four scientists, Suzanne Topalian, Walter Storkus, Benoit van den Eynde and Victor Englehard, described their attempts to actually identify the specific modules in tumors that represent tumor specific antigens. The genetic analysis described by Dr. van den Eynde has indeed led to the identification of the first human melanoma specific antigen recognized by T cells. The general consensus of this session was that additional technological advances would be required to routinely identify antigens expressed by many different human tumors.

The third session described various cell based strategies to utilize the principles of regulation of the immune system in order to activate or augment immune responses against tumor cells. Dr. Martin Cheevers described the evidence that T lymphocytes can recognize portions of oncogenes, the cellular gene products which actually cause the uncontrolled proliferation of cells that define the cancer phenotype. Jack Bennick then described the use of a modified small pox virus as a vaccine strategy to enhance immune responses as well as to test whether cancer cells are suitable targets for activated T lymphocytes. Dr. Drew Pardoll described a gene therapy approach for cancer that use defective viruses to introduce genes into tumor cells that encode the growth and activating factors for the immune responses that under certain circumstances are capable of curing animals of distant deposits of tumors.

The final session described the development of clinical protocols for human cancer based on many principles and vaccine strategies outlined in the earlier sessions of the meeting. Dr. Stan Riddell described immunotherapy for bone marrow transplant patients with cytomegalovirus infections using clones of T cell specific for the cytomegalovirus antigens. He described that this represented a model approach for the use of genetically engineered anti-cancer T cells for adoptive immunotherapy. He also described the use of genetically engineered T cells against the AIDS virus – a clinical protocol which is currently being initiated. Alan Hougton described a number of human melanoma vaccine approaches that use either intact genetically modified cancer cells, or purified human melanoma antigens. Elizabeth Jaffee described the development of clinical trials to use genetically engineered tumor cells for the treatment of metastatic renal cancer.

A number of lively discussions ensued which delineated many of the issues involved in the translation of basic science discoveries to the development of human clinical protocols that will eventually result in meaningful therapies for patients with cancer.

Dr. Pardoll summarized the meeting with a hypothetical scenario of a patient coming to the hospital with cancer in the year 20XX in which a standard laboratory test would be sent off to identify which of a hundred potential tumor antigens this particular patient’s cancer expressed and then the use of a combination of two or three off the shelf vaccine immunization gene therapy strategies that would ultimately result in the cure of this patient’s cancer.

While it is quite clear that such a dream-like scenario is still many decades in the future, it is equally clear that the advances in our understanding of how the immune system is regulated and the ability to use molecular genetics to design human gene therapy approaches makes such hypothetical scenario a reasonable goal to guide future investigation rather than pure fantasy."

Quotes from Participants
“I thoroughly enjoyed my interactions with the participants … and felt a real sense of accomplishment at the conclusion. [The] Foundation is performing an excellent service that I hope will continue, and might serve as a model for the development of scientific conferences sponsored by other groups” -- Victor H. Engelhard, Ph.D., University of Virginia

“It is rare that scientists can meet together under circumstances so conducive to a free exchange of ideas … My sense is that the Foundation has been extraordinarily productive over the years and will continue to provide a unique forum to encourage scientific progress against cancer and other diseases”. -- Suzanne L. Topalian, MD, National Cancer Institute

“It was unusually productive for me … I had already learned a lot from discussions well before the first scientific session … I hope that my contributions will be of some value to the other members of the Forum, but I can say that my discussions with them have already helped me gain some new perspectives even in my own work on autoimmune disease. If in the future I begin a serious program on research in tumor immunity, I will have the Foundation to thank.” -- David Lo, MD, Ph.D., The Scripps Research Institute

“The greatest benefit I got from the Forum is the personal contact with other scientists working in fields related to my research. Although I previously met some of them, it was at very big meetings, with hundreds to thousands of people, without any opportunity for discussion and exchange of ideas that was provided at the Forbeck meeting. This was an invaluable help for me, because now I feel free to contact these colleagues whenever I need their help … proceed with these Forums which are very useful because they are so different, and in many aspects, more productive than classical meetings.” -- Benoit Van den Eyde, MD, Ludwig Institute for Cancer Research, Bruxelles, Belgium

“… a unique and informative conference on cancer. It truly was the best scientific meeting I have been to. I fell that this meeting has resulted in many potential collaborations in the near future … I particularly found the organization of the Forum to be a very useful one … encourages greater discussion and exchange of ideas. In fact, this format helps to enhance the freedom of exchange of data that is usually missing from national meetings.” -- Elizabeth Jaffee, MD, Johns Hopkins Oncology Center

Venue & Travel Information

Hilton Head Island

Travel Forms

TRAVEL FORMS DUE:
October 5, 1992
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 forum. 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 forum. 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 forum 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 forum.
  • Speaker agenda is not sent out prior to the forum. It will be provided upon arrival in the forum 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 forum. Please no children.

What the Foundation Pays

Accommodations and meals are provided by the foundation during the forum. Airfare will be covered only if booked through our travel agent. The Foundation will also cover airport transportation on the forum 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 forum 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 forum. 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:
October 5, 1992
submit abstract

Forum Structure

The structure of the forum 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 forum is relatively short, so please be familiar with papers received prior to arrival.
  • It is very important that you commit to all sessions of the 2 days of the forum.

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 forum starts.

Arrival Day
1:00 PM Arrivals
6:00 PM Cocktails (opt'l)
7:00 PM Dinner
Forum 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
Forum 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 forum. 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 forum.
  • 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.
  • 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

Jack
Bennink
,
MD
National Institutes of Health
Martin
Cheever
,
MD
University of Washington
Victor
Engelhard
,
PhD
University of Virginia
Alan
Houghton
,
MD
Memorial Sloan Kettering Cancer Center
David
Lo
,
MD, PhD
Scripps Research Foundation
Richard
Mulligan
,
PhD
Massachusetts Institute of Technology
Stanley
Riddell
,
MD
Fred Hutchinson Cancer Research Center
Walter
Storkus
,
PhD
University of Pittsburgh
Suzanne
Topalian
,
MD
National Cancer Institute
Benoit
Van den Eynde
,
Ludwig Institute for Cancer Research
Jonathan
Yewdell
,
MD
National Institutes of Health

Forum Scholars

Gregory Plautz, MD
Cleveland Clinic