Abstract
Annually about 400 patients die of renal cell cancer (RCC) in the Netherlands. For patients with metastasized RCC no standard adequate therapy is available. Chemotherapy and hormonal therapy yield less than 10% responses in metastatic RCC. Rapid developments in the field of immunology and molecular biology including the production at large scale of recombinant cytokines and methods for activation and/or expansion of lymphoid populations have led to clinical programs of adoptive cellular immunotherapy. Since 1984 many hundreds of patients suffering from metastatic RCC have been treated with cytokines such as interleukin-2 (IL-2) and a-Interferon (IFN-α) with or without the use of Lymphokine Activated Killer (LAK) lymphocytes [1–4]. Although the response rates are in the order of 25% and survival seems to be prolonged, the severe side effects of these regiments with high dose cytokines prevent this treatment from being considered as standard. Using bispecific monoclonal antibodies (bsmAb), which specifically recognize activation structures on the cytotoxic T-lymphocytes (CTL), such as CD3 on the one hand, and tumor associated antigens (TAA) expressed on the membrane of the tumor cell on the other hand, it is possible to endow the CTL with tumor cell selectivity and reactivity [5–8]. We evaluated this type of treatment in a clinical phase I/II study in 27 ovarian cancer patients with a very poor prognosis. Intraperitoneal treatment with bsmAb (Mov-18) targeted CTL showed a 27% response rate, [9,10] including surgically and histologically documented complete disappearance of all tumor lesions from the abdominal cavity in 4 patients.
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Abbreviations
- Ag:
-
antigen
- JH :
-
immunoglobulin heavy chain joining region
- CTL:
-
cytotoxic T lymphocyte
- GALV:
-
gibbon ape leukemia virus
- mAb:
-
monoclonal antibody
- PCR:
-
polymerase chain reaction
- RCC:
-
renal cell cancer
- scFv:
-
membrane fluorescence intensity
- PMA:
-
single chain variable domain of antibodies
- TAA:
-
tumor associated antigen
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Bolhuis, R.L.H., Willemsen, R.A., Lamers, C.H.J., Stam, K., Gratama, J.W., Weijtens, M.E.M. (1998). Preparation for a Phase I/II Study Using Autologous Gene Modified T Lymphocytes for Treatment of Metastatic Renal Cancer Patients. In: Walden, P., Trefzer, U., Sterry, W., Farzaneh, F., Zambon, P. (eds) Gene Therapy of Cancer. Advances in Experimental Medicine and Biology, vol 451. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5357-1_85
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