ABSTRACT
INTRODUCTION The conceptual basis for therapeutic cancer vaccines was fi rst established in studies that dealt with immunogenic tumor cell lines in mice, more than 25 years ago ( 1 ). Since then, a large body of data generated from mechanistic studies in animal models has confi rmed that both vaccineinduced tumor-specifi c CD4 + T-helper (Th) type 1 and cytotoxic CD8 + T cells (CTL)—as well as B cells-play a major role in controlling tumor growth. Recent results obtained in patients have confi rmed the conclusions from the animal models for the critical role of the immune system’s response against tumors ( 2 – 4 ). Further evidence is provided by ( i ) long-term follow-up studies showing an increased incidence of cancer in immune-suppressed patients ( 5 , 6 ), ( ii ) clinical studies that provide evidence of clinical benefi t of donor lymphocyte infusions after stem-cell transplantation and adoptive transfer of antigen-specifi c T cells ( 7 , 8 ), and ( iii ) studies on large numbers of patients with different tumor types showing that the presence of memory CD4 + Th1 and CTL in tumors is predictive of a benefi cial clinical outcome ( 9 , 10 ).
