tumor cell biology program - Sylvester Comprehensive Cancer Center

light on fundamental principles of effector
gene activation in cytotoxic lymphocytes.
(Lichtenheld)
• A unique peptide with immuno-enhancing
properties has been identified
in a secreted form of human MUC1
and used in vaccination experiments.
This peptide inhibits tumor development
not only in the mammary cells
transfected with the secreted MUC1,
but also provides protection against a
variety of other tumor types. (Lopez)
• The thymuses of mammary tumor
bearers are profoundly involuted and
this is not due to a decrease of the thymocytes
proliferation. A minor increase
of apoptosis was noted, however, the
major cause of this phenomenon appears
to be an arrest at an early stage of
differentiation possibly brought about
by the direct or indirect effects of tumor
derived factors. (Lopez and
Adkins)
• IL-2 during in vitro priming promotes
subsequent engraftment and successful
adoptive tumor immunotherapy by
persistent memory phenotypic CD8 +
T cells. (Malek)
• Heatshock fusion vaccines generate
CD8 CTL without CD4 help; progress
towards novel and efficient tumor specific
vaccines. (Podack)
• CD30 is identified as a major negative
regulator of cytotoxic lymphocytes;
blocking CD30 signals in vivo will dramatically
enhance anti-tumor immune
responses. (Podack)
• Generation of the first murine gene
knock in Florida: CD30-Ligand knock
out in mice will serve as valuable model
for tumor and autoimmunity studies.
(Podack)
• Innovative vaccine trial for lung adenocarcinoma.
(Podack)
• A role for perforin in lymphocyte homeostasis
revealed: cytotoxicity by
perforin is necessary to remove antigenpresenting
cells and turn off T cell activation.
(Podack)
• The 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 (E47) and
surrogate light chains, both of which
are critical to B lineage cell development,
are decreased in aged B cell precursors
provides a molecular basis for
understanding deficient lymphopoiesis
in senescence. (Riley)
• Development of novel antibodychemokine
and antibody-costimulatory
ligand fusion proteins with dual
function and preserved targeting capabilities.
(Rosenblatt)
• Development of a novel strategy for
gene therapy of HIV-1 using mutations
introduced into tRNA LYS3 primers.
(Rosenblatt)
• Demonstration of the potential role for
HSV amplicon vectors in gene therapy
of malignancy, particularly CLL.
(Rosenblatt)
• Demonstration of trafficking and inhibition
by defective HIV-1 as a novel
approach to HIV-1 gene therapy.
(Rosenblatt)
Rebecca D. Adkins, Ph.D.
Associate Professor of
Microbiology and Immunology
DESCRIPTION OF RESEARCH
Newborn animals succumb to infections
and diseases that have little
to no effect in adults. This disease susceptibility
in early life is at least partially
due to the failure to mount protective
immune responses. To understand the
basis for poor responsiveness, Dr. Adkins’
research is focusing on T cell function in
neonates. In particular, the research compares
the T helper (Th) activities that
arise in situ in neonatal versus adult mice.
Th cells can be functionally divided into
Th1 and Th2 subsets. The Th1 subset
produces IFN and mediates delayed-type
hypersensitivity and protection against
intracellular pathogens. The Th2 subset
produces IL-4 and IL-5 and is important
in humoral responses. Immune responses
heavily skewed toward Th1 or
Th2 function can exacerbate infectious
diseases, allergic reactions, diabetes, and
autoimmunity. Consequently, generating
and maintaining the appropriate Th1/
Th2 balance is critical for protective immunity.
This is particularly important for
the very early stages of life, when exposure
to many novel antigens occurs. The
goal of Dr. Adkins’ lab is to understand
how Th1/Th2 responses develop and
persist in early life.
These studies have revealed several
interesting and important differences
between the Th responses of newborns
and adults. First, unlike in adults, newborn
lymph node and spleen cells show
different responses to immunization with
protein antigen; lymph node cells develop
a mature, mixed Th1/Th2 response
whereas spleen cells show exclusive Th2
development. Second, neonatal (not
adult) Th2 function persists for a prolonged
period following a single immunization.
Lastly, animals initially
immunized as neonates are “programmed”
to have Th2-dominant
memory responses, under conditions in
which adults show Th1 dominance.
These observations have made major
contributions to the field of neonatal
immunology for several reasons. First,
they are the first demonstration that the
nature of an immune response in early
life is highly dependent on the site of
initiation of the response (spleen versus
lymph nodes). Second, this laboratory is
unique in studying antigen specific responses
in vivo during the first week of
life. Thus, they have gained important
new insights into the transition from
primary to memory responses in
neonates.
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UM/Sylvester Comprehensive Cancer Center Scientific Report 2002