SCIENTIFIC REPORT 2004 - Sylvester Comprehensive Cancer Center

T U M O R I M M U N O L O G Y P R O G R A M
Frasca, D, Nguyen, D, Riley, RL, and Blomberg,
BB. Effects of aging on proliferation and E47
transcription factor activity induced by different
stimuli in murine splenic B cells. Mechanisms of
Ageing and Development 124:361-69, 2003.
Frasca, D, Nguyen, D, Van Der Put, E, Riley,
RL, and Blomberg, BB. The age-related decrease
in E47 DNA-binding does not depend on increased
Id Inhibitory proteins in bone marrowderived
B cell precursors. Frontiers in Bioscience
8:A110-6, 2003.
Frasca, D, Nguyen, D, Riley, RL, and Blomberg,
BB. Decreased E12 and/or E47 transcription factor
activity in the bone marrow as well as in the
spleen of aged mice. Journal of Immunology
170:719-26, 2003.
Wilson, EL, Sherwood, EM, King, AM, and
Riley, RL. A phenotypically distinct subset of
bone marrow immature B cells exhibits partial
activation, increased survival, and preferential
expression of VhS107. European Journal of Immunology
33:3398, 2003.
HIGHLIGHTS/DISCOVERIES
• Molecular deficits, which underlie dysfunctions
in lymphocyte activity during old age, have yet
to be well characterized. These findings, that
expression of a transcription factor (E2A) and
surrogate light chains, both of which are critical
to B-lineage cell development, are decreased in
aged B-cell precursors, provide a molecular basis
for understanding deficient lymphopoiesis in
senescence.
JOSEPH D. ROSENBLATT, M.D.
Professor of Medicine and
Division Chief of Hematology-Oncology
DESCRIPTION OF RESEARCH
Dr. Rosenblatt’s research focuses on the development
of novel immune therapy and gene
therapy strategies for cancer. Current research has
focused on the potential role of recruitment of
immune effector cells, using the local elaboration
of both constitutive and inflammatory chemokines,
such as secondary lymphoid chemokine
(SLC), DC-CK1, and/or RANTES respectively,
on the development of an anti-tumor response.
Chemokine delivery has been investigated alone,
or in combination with, expression of the costimulatory
ligands CD80 (B7.1) or CD40L.
Several delivery strategies have been investigated
including the use of retroviral vectors, and/or the
use of herpes simplex virus (HSV) amplicon vectors
in several murine tumor models. Preliminary
results suggest that the recruitment of naïve T
cells using SLC is a particularly effective means of
enhancing the anti-tumor immune response, particularly
when combined with CD40L-induced
co-stimulation. This strategy is being formally
investigated using the OT-1 transgenic mouse
model, which has a constitutively expressed T-cell
receptor with defined anti-ovalbumin specificity
and the murine tumors expressing the target ovalbumin
antigen, for effects on tumor-induced tolerance
and the development of systemic
immunity.
In a separate effort, the utility of HSV-derived
helper virus-free amplicons is being tested
for efficacy in augmenting the immunogenicity
and antigen-presenting capability of fresh chronic
lymphocytic leukemia cells (CLL). Both CD40L,
CD80, and/or the tumor necrosis factor (TNF)
ligand family member LIGHT, have been targeted
to fresh CLL cells using the helper free
HSV amplicons. Results suggest the augmented
ability of such CLL cells to present antigen in an
allogeneic mixed-lymphocyte-tumor cell reaction
and/or to serve as stimulatory cells for the deriva-
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