CENTER OF EXCELLENCE IN IMMUNOLOGY

STEERING COMMITTEE MEETING

SUMMARY MINUTES

January 28, 2008

# CENTER OF EXCELLENCE IN IMMUNOLOGY

**STEERING COMMITTEE MEETING**

January 28, 2008

3:00--5:00 p.m.

**Bldg. 31, Room 3A11**

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

> **Members present:** Dr. Robert Wiltrout *(Chair)*
>
> Dr. Jay Berzofsky
>
> Dr. Stephen Creekmore *(Adjunct)*
>
> Dr. Ronald Gress
>
> Dr. Diana Linnekin
>
> Dr. Crystal Mackall
>
> Dr. Marjorie Robert-Guroff
>
> Dr. Steven Rosenberg
>
> Dr. Jeffrey Schlom
>
> Dr. Giorgio Trinchieri
>
> Dr. Thomas Waldmann
>
> Dr. Robert Yarchoan
>
> Dr. Howard Young
>
> **Members absent:**
>
> Dr. Jonathan Ashwell
>
> Dr. Allan Hildesheim
>
> Dr. Jeffrey Lifson
>
> Dr. Douglas Lowy
>
> Ms. Karen Maurey *(Adjunct)*
>
> Dr. Joost Oppenheim
>
> Dr. Ira Pastan
>
> Dr. Alfred Singer
>
> Dr. Dinah Singer
>
> **Guests:** Dr. Rao Bachoti
>
> Mr. Ray Butler
>
> Dr. Laura Hooper

######### Handouts

1.  Agenda

2.  Handout by Dr. Rosenberg (Tentative schedule of 2008 Immunotherapy
    Meeting)

3.  Handout by Dr. Mackall (Proposal for Immunotherapy of Pediatric
    Cancer Meeting)

4.  Handouts by Dr. Waldmann (FDA teleconference minutes and comments by
    FDA)

**Overview**

The Center of Excellence in Immunology Steering Committee (CEI SC)
convened its monthly meeting on January 28, 2008, in Building 31, Room
3A11 with videoconference available in Building 549, Conference Room A,
Frederick. Dr. Robert Wiltrout called the meeting to order at 3:05 p.m.
Dr. Rosenberg provided an update on the 2008 Meeting on *Cancer
Immunology and Immunotherapy.* Dr. Mackall gave an update on the
proposed meeting on the Immunotherapy of Pediatric Cancer. Dr. Linnekin
invited suggestions for potential speakers for a new CCR lecture series.
Dr. Waldmann provided an update on the pre-IND teleconference with FDA
for a phase I clinical trial of IL-15.

**Update on the 2008 Immunotherapy Meeting -- Dr. Steven Rosenberg**

Dr. Rosenberg gave an update on the meeting "Cancer Immunology and
Immunotherapy: Realizing the Promise" scheduled on September 11 &12,
2008 in Masur auditorium with videocast available in Lipsett auditorium
if there is an overflow. The emphasis of the meeting is on realizing the
promise of immunotherapy and thus on work directly related to clinical
trials of immunotherapy in humans. There are 28 speakers, 13 from the
NCI. NCI speakers will be acting as the moderators of the sessions.
There will be two sessions on the first day, immunotherapies based on T
cell transfer or gene modification of lymphocytes, and antibody-based
therapies. There will be three sessions on the second day,
transplantation-based therapies, vaccine-based therapies, and immune
modulatory molecules. The committee felt that the talks should be
limited to 20 minutes followed by a discussion for 10 minutes and that
the session moderators insist that the speakers do not exceed the time
limit. It was agreed that meeting would start earlier by half hour with
an increase in break time to facilitate interaction between speakers and
attendees. About 500­--600 attendees are expected.

**Proposal for Immunotherapy of Pediatric Cancer Meeting -- Dr. Crystal
Mackall**

Dr. Mackall said that there is a need for a pediatric immunotherapy
meeting as this research community does not have any specific
organizations or consortiums. Dr. Mackall and colleagues would like to
put together a meeting to bring members of this research community
together. The meeting is proposed to be on September 9--10 so
participants can attend this meeting as well as the "Cancer Immunology
and Immunotherapy" meeting on September 11--12. The two meeting would be
complementary and very little overlap of presentations will occur. This
small meeting will be held at Cloister Center, with an expected
attendance of 50--80 scientists. There will be two sessions on day 1 and
two on day 2.

**Discussion on potential speakers for new CCR lecture series -- Dr.
Diana Linnekin**

The seminar series will start in the fall and suggestions for speakers
are invited. The monthly seminars will cover a wide scope of research to
include but not be restricted to immunology. These will not overlap with
the clinical grand rounds, or other ongoing lecture series. They will be
held on the fourth Monday of the month from 3--4 p.m. The possibility of
tying this series with clinical grand rounds and awarding CME credits
was discussed.

**Update on moving IL-15 toward Phase I trial -- Dr. Thomas Waldmann**

Dr. Waldmann provided an update on the teleconference with the FDA on
November 30, 2007 on the pre-IND submission for a proposed clinical
trial of IL-15. The FDA has been very helpful and supportive and
suggested several changes to the protocol.

The FDA stated that sets of 5 Rhesus macaques (0, 20, 50 and 200 µg/kg
everyday for 12 days, the same schedule as in humans) are required and
an autopsy needs to be performed in half the animals 1--3 days after the
last dose, and another autopsy at 43--51 days. Permission from the FDA
is not required to do a study in monkeys but an approved monkey study is
needed for the review of a clinical study. So if the study is conducted
without an FDA approval, it would have to be repeated according to FDA
stipulations. A toxicology analysis is required for the first study in
humans of any biologically active substance.

The FDA also stated that the study needs to be staggered, i.e., a set of
four animals are to be tested first, one at each dose and the results
submitted to the FDA before it can be extended to the 20 animal study
originally planned. The vials of IL-15 material would arrive at the
animal facility on January 29 and the study would start on February 4.
The monkeys are chair-trained to facilitate 12 daily doses because they
cannot be anesthetized more than three times a week. The clinical part
will be done in part by Dr. Fleisher's group or a contractor. The
hardest part is the auto-immune study for which help will be obtained
from a veterinarian.

A total of 230 mg of IL-15 (265 vials of 900 µg each) will be received
and the study needs 207 mg. The material available for others is 50 mg
of material that has an extra amino acid, arginine on 20% of the cells.
The material has full biological activity and will be available for any
NCI or NIAID researchers who want to conduct studies on IL-15. Another
lot will be paid for by NIAID and will be used for continuous (three
times daily) infusion studies by the NIAID. Dr. Waldmann mentioned that
in the case of IL-2 and IL-7, there is a precipitous drop in plasma
concentration. For IL-15 there is a precipitous drop in the serum
concentration in the absence of IL-15R. In the presence of IL-15R there
will be significant concentrations even after 10 days. Therefore, it is
not clear if multiple daily infusions would give us additional
information. The dosage schedule in the proposed trial will be one
infusion everyday for 12 days.

Dr. Waldmann hopes that PRMC and IRB will issue a provisional approval
for the study based on the toxicological study and also critique and
suggest any modifications.

**General:**

The CEI SC expressed concern over the long delays in FDA approvals of
clinical trials particularly in relation to trialsls impacting
terminally ill cancer patients for whom time is of the essence. The
committee sought to discuss with the NCI leadership the option of
approaching FDA to secure some new procedures to hasten the process if
possible. Dr Wiltrout indicated he would talk with Dr Niederhuber to
explore the possibilities of facilitating FDA approval of NCI clinical
trials.

The meeting adjourned at 4:15 p.m.

**Next Meeting: March 31, 2008**

**Location: Building 31/Room 3A11**

**Videoconference to Frederick: Building 549 Executive Board Room**