Biotecnología Aplicada 1998;15:259-266
Cancer and autoimmunity: Building the bridge
Agustín Lage
Code Number: BA98043
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Resúmenes seleccionados de las conferencias dadas en la
tercera edición
del encuentro "Inmunoterapia en los 90", Centro de
Inmunología Molecular, La
Habana, Cuba, abril 20-24, 1998.
Selected abstracts of lectures given at the 3rd edition of the
meeting: "Immunotherapy in
the Nineties", Center of Molecular Immunology, Havana, Cuba, April
20-24, 1998.
Let's try to help the readers to capture the
intentionality behind this
particular gathering of autoimmunity researchers and cancer
researchers which has taken place
at the Center of Molecular Immunology (CIM) in Havana, Cuba, since
1994.
The Immune Response to Human Cytomegalovirus and to Recombinant
HCMV Antigens.
Application to the Construction of a Subunit Vaccine
C Davrinche, JL Davignon, E Prieur, J Vaz-Santiago, D
Betbeder, C de
Preval
Human cytomegalovirus is a member of the b
herpes
subfamily. In the population of industrial countries 50% of the
population is infected. Human
cytomegalovirus (HCMV) becomes latent after primary infection which
is usually
asymptomatic in healthy individuals. However, in immunoincompetent
individuals infection
can be very severe. In transplant patients HCMV can cause graft
rejection and acute
pneumonia. In cancer and AIDS patients it is the cause of retinitis
leading to blindness, as well
as of colitis, gastritis and pneumonia. Primary infection during
pregnancy can cause important
birth defects, including neurological disorders associated with
mental retardation and sensorial
disabilities.
Th Lymphocyte Classes in Immune Regulation: Organizing Molecules
and Cells to Build
up Immunity
Jorge Carneiro
The class differentiation and cross-regulation
of Th lymphocytes, for
which the Th1/Th2 dichotomy is the main paradigm, is believed to
play a major role in
determining the behavior of the immune system, and in the fate of
the immune response in
particular. It might provide the cellular basis for dominant or
infectious tolerance, and in this
way it may represent a target for autoimmune therapy or the control
of organ transplantation.
Natural Antibody Surveillance of Activated, Preneoplastic and
Neoplastic Cells
Contributes to Homeostasis of the Organism
DA Chow, H Wang, ZY Zhang
Extensive evidence, including passive transfer
studies supports a role
for polyclonal serum natural antibody (NAb) acting as a mediator of
natural resistance against
tumors in mice However, little is known about their mechanisms of
action or about the
phenotype of susceptible cells. The expression of NAb binding
structures appears to be
elevated by constitutive increases in the basal activation of PKC
in both a
ras-transformed and a preneoplastic rat PKC-B1
overexpressing model in 10Ti C3fI
fibroblasts.
Human scFv against the Epithelial Tumor Marker MUC-1 Isolated
from a Phage
Display Library
Cindy Wong, Jean-Pierre Mach, Ricarda Finnern
Efforts are being made to develop anti-cancer
agents with the ability
to distinguish between normal and tumor cells.
Analysis of Anti-anti-idiotypic Responses Induced by
NeuGc-containing Ganglioside
Anti-idiotypic Monoclonal Antibodies
AM Vázquez, R Pérez, A Pérez, AM
Hernández, M
Alfonso, G Bombino, I Beausoleil
Five mouse anti-idiotypic (Ab2) MAbs were
generated against a
mouse anti-NeuGc containing-ganglioside MAbs (P3 MAb). These IgG1
Ab2 MAbs were able
to block the binding of the Ab1 MAb to the NeuGcGM3 ganglioside and
to a breast human
carcinoma cell line recognized by P3 Mab.
Dendritic Cells Interactions with Fibronectin and Endothelial
Cell
C Jancin, E Chuluyan, A Morelli, A Larregina, M Saracco, M
Barboza, L
Fainborn
Dendritic cells (DC) are professional antigen
presenting cells that
can prime naive T helper lymphocytes and elicit cytotoxic T
lymphocyte responses to soluble
antigens. In vitro antigen-pulsed DC can induce
antigen-specific T cell responses,
supporting the potential use in clinical immunotherapy. Indeed,
tumor regression has been
observed after vaccination with DC pulsed with lymphoma specific
idiotypes.
Immuno Modulatory Effects of Multispecific Anti-idiotype
Antibodies on Cell Mediated
Immunoresponse
A Macías, S Arce, R Bolaños, J León, L
Suárez, R
Pérez, A Lage
The manipulation of idiotypical interaction has
shown to be of real
value, as suggested by the success reported for the treatment of
various autoimmune diseases
with a human IgG pool, containing an important fraction of
idiotipically connected natural
autoantibodies.
Prediction of Antibody-ligand Complexes: the Ligand Selects the
Proper Binding Site
Geometry
Ernesto Moreno
Several approaches have been developed to dock
relatively small
ligands to protein receptors. Few of them include some degree of
protein flexibility. In this
study, a new method was developed to screen a large amount of
receptor conformations for
ligand binding.
Lessons from Transplantation Tolerance: Relevance to
Regulating Antitumour
Immunity
Robert Lechler
In many strain combinations, passenger
cell-depleted rodent organ
allografts are accepted in the absence of any immunosuppression,
while allografts containing
bone marrow-derived antigen-presenting cells are promptly rejected.
These observations
highlighted the crucia1 distinction between antigenicity and
immunogenicity.
Therapeutic Manipulations of Natural Autoreactivity
E Montero, F Quintana, A Rojas, I Beausoleil, E Renjifo, JF
Amador, R
Pérez, A Lage
The autoimmune recognition of tumor antigens is
emerging as a
paradigm with implications to induce tumor immunity as
autoimmunity. From this view, the
main question is essentially how to break the state of immune
tolerance or ignorance in order
to induce tumor rejection.
Immunity to Mutant p53 and Tumor Rejection Induced by Idiotypic
Immunization
Pedro J Ruíz, Roland Wolkowicz, Ari Waisman, David L
Hirschberg, Pnina
Carmi, Netta Erez, Hideki Garren, Johannes Herkel, Marcela Karpuj,
Lawrence Steinman,
Varda Rotter, Irun R Cohen
The tumor suppressor gene p53 is mutated in
tumors arising
in various organs, and the p53 protein is often over-expressed in
tumor cells. Hence, the p53
molecule might serve as a common tumor-associated antigen.
N-Glycolylated Ganglioside Vaccine for Breast Cancer Therapy:
Advantages of
Combining Hydrophobic Xenogenization with Heterophile Character
L Fernández, A Carr, G Marquina, Z Mazorra, F
Estévez, A Mullet,
O Valiente, R Pérez
Although thousands of patients have received a
variety of cancer
vaccines over the last 25 years, significant tumor responses are
only occasionally observed.
Many tumor antigens have been described at molecular level in these
years but the main
problem with human cancer antigens is their poor immunogenicity.
This is particularly true for
most carbohydrate tumor antigens, which are both Tcell independent
and "self" antigens.
Generation of Responses to Cryptic Epitopes by
Interleukin-6-treated Dendritic Cells
PCL Beverley, H Drakesmith, D O'Neil, S Schneider, E
Sercarz, B Chain
Identification of the target antigens of
cytotoxic T lymphocytes in
murine and human tumours, has shown that many are unaltered tissue
specific differentiation
antigens. The majority of Tcells with high affinity for self should
be deleted in the thymus so
that it might be difficult to generate a powerful immune response
against epitopes of these
molecules normally produced by antigen processing. However, here we
show that under
experimental conditions responses to cryptic epitopes can be
generated.
Dominant Tolerance in an Immune Network Model
Kalet León, Jorge Carneiro, Enrique Montero, Rolando
Pérez,
Agustín Lage
Here we summarize our results in the study of
immunological
tolerance throughout the development of a mathematical model of the
immune system. Our
general approach is to conceive tolerance as an active dominant
phenomena related, at least
partially, to the intrinsic non-linear dynamics of the immune
system, which is a consequence of
complex specific interactions involving variable region molecules.
Epidermal Growth Factor Receptor and the o-Lynked Glycoprotein
Carbohydrate Chain
Tumor Associated Antigen ior C2 as Potential Targets for Cell
Directed Radiation
Therapy
Normando Iznaga-Escobar, Tania Crombet, Juan Félix
Amador, Rolando
Pérez
The use of antibodies as targeting agents for
the delivery of
radioisotopes to tumors is an appealing concept that has been
receiving widespread attention
since the advent of monoclonal antibody technology. Cell directed
radiation therapy (CDRT or
Radioimmunotherapy) has the potential of killing cells within a
tumor whether or not they
express the antigen to which the antibody binds. However,
characteristics and distribution of
target antigens remain crucial considerations in the development of
monoclonal antibody based
therapies.
EGF-cancer Vaccine: a New Immunotherapeutical Approach
G González,1 B Sánchez, I
Beausoleil, OL Pardo, JL
García, T Crombet, M Catal, JC Hernández, V Mirabal,
Y González, P
Marinello, A Domarco, G Guillén, R Pérez, A Lage
The possibility of inducing the immune system to
recognize
self epidermal growth factor (EGF) was studied in mice and monkeys.
Mice produced
antibodies against murine EGF (mu-EGF) when immunized with mu-EGF
linked to a carrier
protein. Anti-EGF antibody response showed immunological memory and
was an IgG isotype.
Immune sera inhibits binding between EGF and its receptor in an
in vitro competence
assay.
Copyright 1998 Elfos Scientiae
