10.5: med/cancer/cellular immunotherapy/
detect a cancer cell's CD 19 protein:
time.mag aug 21 p36:
Dr. Carl June developed a method for growing
chimeric antigen receptor T cells;
that is reprogramming a person's T cells
to detect a cancer cell's CD 19 protein,
reducing risk of autoimmunity disorder
while increase chance of a cure.
11.6: BMJ. 2001:
"Cellular immunotherapy" consists of
giving the patient cells that stimulate antitumour activity
(tumour and dendritic cell vaccines)
or that have intrinsic antitumour activity
(autologous and allogeneic lymphocytes).
The aim is to harness potent immunological weapons
to destroy cancer cells.
Reasons for the failure of immune responses:
# Impaired tumour recognition by immune cells:
Variable expression of tumour antigens
Loss of expression of class I major histocompatibility complex,
resulting in T cells failing to recognise tumours
# Poor tumour immunogenicity:
Many tumour antigens are self antigens
and as such are poorly recognised by T cells;
Lack of costimulatory molecules on tumour cells,
which results in failure to stimulate T cells.
# Tumour “counterattack”:
Tumour cells secrete immunosuppressive cytokines
(transforming growth factor β or interleukin 10, for example);
Molecules expressed on the surface of tumour cells
(for example, Fas ligand) may induce lymphocyte death;
Evolution of variants of tumour cells
that do not express antigens.
.
Allogeneic lymphocyte therapy:
A potent graft versus leukaemia effect
may be mediated by donor T cells that
recognise disparities between donor's and host's
tissue histocompatibility antigens
as well as tumour antigens.
Infusions of allogeneic donor leucocytes led to
clinical responses in 60-80% of patients
with chronic myeloid leukaemia
who had relapsed after allogeneic transplantation.
Recent reports suggest that a graft versus tumour response
may be successfully induced against solid tumours
such as renal cell carcinoma.
Unfortunately, use of allogeneic lymphocytes
is frequently accompanied by graft versus host disease,
in which donor T cells recognise the host tissue as “foreign.”
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