K Bartnes1. 1. Avdeling for hjerte-/lunge-/karkirurgi Regionsykehuset i Tromsø 9038 Tromsø. kirkrb@rito.no
Abstract
BACKGROUND: Due to acquired mutations, the protein composition of malignant tumours is distinct from that of normal cells to which the immune system is tolerant. Mobilisation of the patient's immune system against malignant cells remaining after conventional treatment is an attractive therapeutic option since lymphocytes respond with high sensitivity and specificity to non-self. MATERIAL AND METHODS: The potential of cancer vaccines targeted to T helper cells is discussed on the basis of published data including the author's studies. RESULTS: T helper cells kill cancer cells by direct cell-cell contact, stimulate other cytotoxic effector cells and respond to autologous tumour antigens like HER-2/neu (mammary and ovary cancer), tyrosinase (malignant melanoma), p21 ras (colorectal and pancreatic cancer), BCR-ABL (chronic myeloid leukaemia) and immunoglobulin (B-cell lymphoma). HER-2/neu and tyrosinase are not mutated, p21 ras and BCR-ABL represent a restricted set of mutations, and genetic variants of immunoglobulin can be characterised by hybridoma technology. INTERPRETATION: Targeted screening can, in a large number of cancer patients, identify peptide sequences potentially useful for therapeutic immunisation. Peptides can be designed to combine immunogenicity in the individual patient with proteolytic resistance, and are presently being tested as cancer vaccines.
BACKGROUND: Due to acquired mutations, the protein composition of malignant tumours is distinct from that of normal cells to which the immune system is tolerant. Mobilisation of the patient's immune system against malignant cells remaining after conventional treatment is an attractive therapeutic option since lymphocytes respond with high sensitivity and specificity to non-self. MATERIAL AND METHODS: The potential of cancer vaccines targeted to T helper cells is discussed on the basis of published data including the author's studies. RESULTS: T helper cells kill cancer cells by direct cell-cell contact, stimulate other cytotoxic effector cells and respond to autologous tumour antigens like HER-2/neu (mammary and ovary cancer), tyrosinase (malignant melanoma), p21 ras (colorectal and pancreatic cancer), BCR-ABL (chronic myeloid leukaemia) and immunoglobulin (B-cell lymphoma). HER-2/neu and tyrosinase are not mutated, p21 ras and BCR-ABL represent a restricted set of mutations, and genetic variants of immunoglobulin can be characterised by hybridoma technology. INTERPRETATION: Targeted screening can, in a large number of cancerpatients, identify peptide sequences potentially useful for therapeutic immunisation. Peptides can be designed to combine immunogenicity in the individual patient with proteolytic resistance, and are presently being tested as cancer vaccines.