Cancer Immune Therapy Edited by G. Stuhler and P. Walden ...

12.2 Cancer Immunotherapy Strategies with HSPs
Fig. 12.2 Cancer immunotherapy strategies with HSPs.
Three general strategies are explored for immunotherapy
of cancer by HSPs. (1) Autologous tumor-derived HSPs
can be purified and re-injected into a patient to elicit tumor-specific
immunity. (2) If the tumor antigen is defined,
the HSP±tumor antigen complex can be generated
either covalently or non-covalently and used as a vaccine
to generate antigen-specific immunity. (3) Whole tumor
cells engineered to express high levels of HSPs or express
HSPs ectopically (secretion or cell surface expression)
are used as tumor vaccines.
coma, prostate or breast cancers (Tab. 12.1). The first pilot trial for the treatment of
human malignancy showed that this approach is safe and feasible [56]. In this trial,
16 patients with various advanced malignancies (seven gastrointestinal tract, one
pancreatic, two hepatocellular, three thyroid, one breast, one mesothelioma and one
unknown primary), which had become refractory to established therapies, were treated
with autologous tumor-derived gp96. Patients were injected subcutaneously (s.c.)
with 25 mg autologous gp96 once a week for 4 weeks. After each vaccination, patients
were carefully monitored clinically and serologically. No unacceptable toxicities or
autoimmune phenomenon were observed. Three patients reported mild hot flashes
between 30 and 48 min after immunization, without the need for medical intervention.
Of these, two experienced hot flashes after each immunization, while one ex-
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