CENTER OF EXCELLENCE IN IMMUNOLOGY

STEERING COMMITTEE MEETING

SUMMARY MINUTES

May 20, 2005

# CENTER OF EXCELLENCE IN IMMUNOLOGY

**STEERING COMMITTEE MEETING**

May 20, 2005\
10:00 a.m.--noon

**Bldg. 31, Room 6A35**

**Videoconference to Frederick Bldg. 549, Room B**

> **Members present:** Dr. Robert Wiltrout *(Chair)*
>
> Dr. Jonathan Ashwell
>
> Dr. Jay Berzofsky
>
> Dr. Allan Hildesheim
>
> Dr. Diana Linnekin
>
> Dr. Anatoli Malyguine *(Adjunct)*
>
> Ms. Karen Maurey *(Adjunct)*
>
> Dr. Steven Rosenberg
>
> Dr. Jeffrey Schlom
>
> Dr. Thomas Waldmann
>
> Dr. Robert Yarchoan
>
> **Members absent:** Dr. Stephen Creekmore *(Adjunct)*
>
> Dr. Ronald Gress
>
> Dr. Jeffrey Lifson
>
> Dr. Douglas Lowy
>
> Dr. Crystal Mackall
>
> Dr. Ruth Nussinov
>
> Dr. Joost Oppenheim
>
> Dr. John Ortaldo
>
> Dr. Ira Pastan
>
> Dr. George Pavlakis
>
> Dr. Marjorie Robert-Guroff
>
> Dr. Dale Shoemaker
>
> Dr. Alfred Singer
>
> Dr. John Wigginton
>
> **Guests:** Dr. Petra Delgado
>
> Mr. Ray Butler

**CENTER OF EXCELLENCE IN IMMUNOLOGY**

# STEERING COMMITTEE MEETING

May 20, 2005

ACTION ITEMS

-   **Dr. Diana Linnekin**

    -   Distribute to CEI SC members the presentation to the BSC about
        the CEI and request comments.

-   **Ms. Karen Maurey**

    -   Contact Dr. Maureen Wilson to outline the steps that CCR can
        take to accelerate the current CRADA ethics review process.

    -   Prepare a fact-sheet defining the different types of
        collaborative agreements, their specific requirements, and their
        approximate processing times.

-   **CEI SC Members**

    -   Provide Dr. Linnekin (<dlinnekin@ncifcrf.gov>) with information
        about successful immunotherapies pioneered at CCR, including the
        number of patients treated and the impact of these therapies on
        the research community.

######### Handouts:

Agenda

OVERVIEW

The Center of Excellence in Immunology Steering Committee (CEI SC)
convened its monthly meeting on May 20, 2005, at 10:00 a.m. Dr. Bob
Wiltrout provided an update on recent activities conducted by the Center
for Cancer Research (CCR) Office of the Director (OD), including a
presentation to the joint Board of Scientific Counselors (BSC) and the
development of new initiatives. A discussion about navigating challenges
to the immunology community at CCR and how to overcome barriers to
translational research followed.

UPDATE ON CCR ACTIVITIES

Dr. Wiltrout provided CEI SC members with an update on recent activities
conducted by the CCR OD with regards to immunology at the CCR. He
mentioned that he did a presentation about the CEI at the March BSC
meeting and that it had been well received. Briefly, the presentation
underscored immunology research as an area of strength at the CCR, with
a critical mass of world-class investigators conducting complementary
research in basic, translational, and clinical immunology. The BSC was
impressed with the number of researchers trained in CEI laboratories who
currently hold high-level positions in academia and industry.
Dr. Wiltrout mentioned similar approaches can be used for future
presentations to the BSC and the NCI Director on other strong research
communities at the CCR. For example, the July BSC meeting will focus on
molecular targets, genetics and genomics, and advanced technologies, as
well as the clinical program. CEI SC members may be requested to present
at upcoming BSC and other meetings. Dr. Steven Rosenberg is scheduled to
present his research on cell therapy to the National Cancer Advisory
Board (NCAB) in June. In addition, Drs. Wiltrout and Helman will provide
the NCAB with an overview of CCR's clinical program. Dr. Wiltrout's goal
is to prevent "across-the-board" funding cuts and to increase and
complement areas of strength in the CCR research portfolio. Two of these
areas, carcinogenesis and immunology, will be combined in a future CCR
research initiative on inflammation in cancer that will involve
collaborations between carcinogenesis researchers, such as Drs. Curtis
Harris, Stuart Yuspa, and Snorri S. Thorgeirsson, and basic
immunologists in Frederick, led by Drs. John Ortaldo and Joost
Oppenheim. Details of this project will be defined at a meeting to be
held at the end of May. The project plans will subsequently be presented
to Dr. von Eschenbach; the initiative will be presented to the BSC in
fall 2005.

Dr. Wiltrout clarified the BSC evaluation criteria for CCR
investigators. Review of senior, established investigators is
predominantly retrospective; review of tenure-track investigators takes
into account both past accomplishments and future research plans. The
review process is being modified to properly evaluate individual
contributions to multidisciplinary research teams.

Dr. Wiltrout stressed that Dr. von Eschenbach is fully supportive of
immunology research within the CCR and strongly encourages projects that
increase the visibility of this research area. Two examples are the *CEI
Report,* which is in preparation and the CEI-sponsored conference,
*Translational Immunology Related to Cancer,* to be held September
22--23, 2005, in the Masur Auditorium, Building 10, NIH. Dr. Rosenberg
thanked Jeff Schlom for his hard work organizing the conference. The
program and registration forms are available at
<http://web.ncifcrf.gov/events/tirc/default.asp>.

Dr. Wiltrout indicated that a meeting was held on April 13, 2005, in
Building 41 to provide Dr. von Eschenbach with an overview of some large
thematic research areas within the CCR. The meeting was organized by
Dr. Gordon Hager and included presentations from both junior and
established investigators in live cell imaging; host genetics,
inflammation, and therapy; drug discovery; and lymphoma diagnosis and
treatment. Dr. Wiltrout indicated that this meeting was a success and
that similar meetings will be planned for the future. An advantage of
this venue is that it provides the NCI OD an opportunity to stay abreast
of exciting research at the CCR, as well as facilitating interactions
among investigators.

VISION OF THE FUTURE OF IMMUNOLOGY AT CCR

Two documents highlighting research at the CCR are currently in
preparation: the *CEI Report* and the *CCR Vision* brochure.
Dr. Linnekin is gathering information for a section of the *CEI Report*
describing future directions and challenges faced by the immunology
community in the CCR. In the responses received thus far, several PIs
considered it critical that the NCI produce clinical-grade reagents more
quickly and be less encumbered by regulatory processes. Dr. Tom Waldmann
noted that limited financial and scientific resources are delaying
production of clinical-grade reagents originated at the CCR. He believes
that the budget allocated to CCR investigators by the Biopharmaceutical
Development Program (BDP) is inadequate. He explained that the Clinical
Product Review Committee no longer has funds to support these projects.
In addition, the BDP does not have the scientific resources to perform
some standard studies required for clinical development of an agent
(e.g., pharmacokinetic and toxicology studies). Having access to
contractors other than BDP might allow faster development of promising
agents, such as IL‑15.

It was noted that although the IRP played a role in the discovery and
development of IL‑15, Amgen holds the patent on this molecule and is not
currently developing it for clinical use. It was suggested that NCI take
the lead in developing "orphaned" molecules like IL‑15 that, on a
scientific basis, have potential in cancer treatment. Dr. Wiltrout will
explore potential funding mechanisms from CCR and NCI for developing
IL‑15. Dr. Waldman added that NIAID could also contribute, as
Dr. Clifford Lane, NIAID's Acting Deputy Director, is interested in
developing IL‑15 for AIDS treatment.

Dr. Alan Hildesheim pointed out that there is a pressing need for cancer
prevention immunotherapies. Populationwide vaccinations are not possible
in cancer prevention, but vaccinating individuals who show precancerous
signs (abnormal mammograms, colon polyps, or cervical dysplasia) might
have a significant impact on public health; for instance, any viral
cancer could be targeted. Dr. Berzofsky added that the HPV vaccine can
be used for cancer prevention as well as to block progression of
preneoplastic lesions; he noted that many functions of the E6 and E7
proteins were defined at CCR. There is also expertise on the
HTLV-1virus, which was discovered at CCR. Dr. Rosenberg observed that
the targets for preventive immunotherapy will likely be identified
through efforts at treating patients with metastatic disease. Dr. Schlom
summarized ongoing preclinical studies for prevention of prostate cancer
conducted by Dr. Peter Greenwald, Director of the Division of Cancer
Prevention, and recommended requesting Dr. Greenwald's input in the
event the CCR decides to establish a cancer prevention program.
Dr. Wiltrout noted that prevention of cancer in patients with
precancerous lesions will require a significant effort in basic science
and the CCR could certainly play a role in research preventing specific
cancers that are chosen as targets.

Dr. Rosenberg commented that many CCR presentations oversell the promise
of novel immunologic agents while underselling the results obtained in
the clinic. He suggested emphasizing that the scientific concept of
immunotherapy works and that every effective immunotherapy in solid
tumors has been developed by the CCR. Dr. Schlom added that the CCR
should continue to develop innovative, promising strategies for
immunotherapy, a feature that distinguishes the CCR from the Cancer
Centers. For future presentations, Dr. Wiltrout recommended that the CCR
take appropriate credit for real successes and then frame future promise
in a different context---i.e., stating that building on previous
successes, the critical mass of outstanding immunologists at CCR will
continue advancing immunotherapy. Dr. Linnekin will request members to
provide her with data about successful immunotherapies, including number
of patients treated with these therapies, to show their impact.

Dr. Berzofsky mentioned that the new ethics review process for
Cooperative Research and Development Agreements (CRADA) is slowing
translational research. Ms. Karen Maurey agreed and explained that the
turnaround time for CRADA approval by the Ethics Committee is now about
6 months. The ethics review process has more levels of scrutiny, and
CRADAs can no longer be sent for review to the CRADA Subcommittee before
they are approved by the Ethics Committee. PIs' financial reports have
to be complete and up to date before the ethics review. Some senior PIs
must be cleared by the NIH before their CRADAs can be reviewed.
Ms. Maurey's office and the CRADA Subcommittee are reviewing the PIs'
CRADA portfolios in great detail to avoid overlapping research scopes.
She anticipates that unless the new ethics guidelines are revised, the
CRADA review process will become more cumbersome. Last year, the
Technology Transfer Office executed half its usual number of NCI CRADAs.
Not all unexecuted CRADAs can be accounted for as pending or held by the
Ethics Committee; a smaller number of CRADAs were requested and
initiated. Because the new ethics regulations are affecting interactions
with industry, it is critical that companies be informed that
collaborations are not banned under the new ethics regulations; on the
contrary, they are encouraged.

Asked about what could be done at the NCI level to address this problem,
Ms. Maurey recommended contacting Dr. Maureen Wilson, NCI Ethics
Coordinator. With the new regulations, it is unclear whether Dr. Wilson
can approve some CRADAs or whether all agreements must be approved by
Dr. Raynard Kington, NIH OD, Ethics Deputy Counselor. Dr. Wiltrout is
willing to discuss the problem with the NCI and NIH leaderships.

Dr. Berzofsky suggested that differentiating between agents used for
basic research and those used in clinical trials may help address the
problem, but Ms. Maurey explained that Clinical Trial Agreements (CTAs)
may then have to undergo ethics revision as well. CTAs undergo no
conflict-of-interest review and no NIH oversight; the difficulty for
industry is that a CTA does not provide licensing. CTEP favors CTAs for
its projects. Ms. Maurey's office is trying to use CTAs and Material
Transfer Agreements (MTAs) rather than CRADAs because these agreements
are approved faster; however, NCI cannot accept funding from industry
collaborators under these agreements. Dr. Schlom asked Ms. Maurey to
prepare a brief fact sheet defining the different types of agreements,
their specific requirements, and their approximate processing times.

Recapitulating the discussion, Dr. Wiltrout reiterated his commitment to
addressing the ethics approval problem and asked Ms. Maurey to discuss
the situation with Dr. Wilson. Dr. Wiltrout proposed eventually
involving other CEI SC members in the discussion in order to generate
momentum as well as, if necessary, convene a meeting with Dr. Kington.

The meeting adjourned at 11:50 a.m.

**Next Meeting: June 20, 2005**\
**Location: NIH, Bldg. 31, Room 7A24**

**Videoconference to Frederick Bldg. 549, Conference Room B**