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INTRODUCTION

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It has been a dream for a long time for immunotherapists to treat and cure patients with malignancies by using immunotherapeutic drugs.

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The first attempt to vaccinate patients with cancer dates back to the end of the 18th century (1777) when the surgeon to the Duke of Kent, Dr. Nooth, immunised himself with tumour cells with the aim of preventing cancer, a brave and visionary experiment.

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At the beginning of the 20th century, Paul Ehrlich coined the term ‘The Magic Bullet’, i.e. antibodies that could trace invaders and destroy them. During the first half of that century, there were several reports on a limited number of patients with lymphomas and chronic lymphocytic leukaemia (CLL) treated with serotherapy. De Carvalho [1] treated patients with leukaemia and lymphoma with hyperimmune gamma globulin raised in horses and donkeys against leukaemic cells. Some major and long-lasting responses were seen. CLL patients were also treated with isologous sera against normal lymphocytes. Healthy individuals were immunised with allogeneic lymphocytes and plasmapheresed. Sera with high titres of cytotoxic antibodies were transfused to end-stage CLL patients. In some, there were short falls in the peripheral blood white cell count [2]. In Sezary’s syndromes, anti-thymocyte globulin and anti-lymphocyte globulin were shown to be effective in some patients [3, 4].

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Modern immunotherapy of haematological malignancies, especially lymphoid disorders, began in the early 1970s. An overview of early clinical studies is presented in this chapter with the focus on interferons, monoclonal antibodies (MAbs) and vaccines.

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INTERFERONS

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Interferons are cytokines which have been shown to have many effects on the immune system. They were found to stimulate the activity of natural killer (NK) and T cells, as well as up-regulate surface structures on tumour cells and immune cells, such as tumour antigens and major histocompatibility complex (MHC) molecules. We have since learnt a lot more about effects of interferons on other systems, but their effects on the immune system were the main reasons why interferons were considered candidates for immunotherapy.

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During the 1960s, techniques for the production of natural interferons were established and large amounts of natural interferons could be produced by infection of buffy coat white cells with Sendai virus [5] as well as spontaneously produced by the lymphoma cell line Namalwa [6]. The Finnish virologist Cantell and his colleagues [5] pioneered the production of natural α-interferon.

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The first report on treatment of patients with multiple myeloma using natural α-interferon was published in 1979 by Mellstedt and colleagues [7] and showed tumour responses (>50% reduction of the M-component) in preferentially IgA and Bence Jones’ myeloma, a finding which was later confirmed for natural α-interferon but not for recombinant α-interferon [8]. In a subsequent randomised study, Mellstedt and colleagues [9] showed that natural ...

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