Monoclonal Antibodies for the Immunotherapy of Solid Tumours

Abstract

More than 80% of all cancers are caused by solid malignancies. More than 90% of these tumours are of epithelial origin. The main principles in tumour treatment are surgery, radiotherapy, chemotherapy or combinations of these. Complete surgical removal of the tumour is the most effective therapy for solid malignancies. Recent advances in early cancer detection led to a higher rate of resectable primary tumours and therefore prognosis will be determined especially by metastasis. Even in early stages some tumour cells may disseminate for example into the bone marrow. If these occult metastasis get evident they are mostly incurable by surgery and often highly resistant to chemotherapy. Developing new therapeutic agents to destroy these resting cells is a major challenge for the improvement of cancer therapy in the future. Advances to reach these goals were made in immunological therapies with monoclonal antibodies (MABs). These MABs are for example directed against tumor-associated antigens (TAAs). By binding selectively on tumor cells they can activate immunological effector mechanisms, e.g. antibody dependent cell cytotoxicity (ADCC) or complement mediated lysis. Other mechanisms are the blocking of inhibiting molecules to re-activate anergic tumor infiltrating lymphocytes (TILs). Furthermore growing tumours depend on oxygen supply, i.e. on effective neovascularisation. Antibodies against VEGF are able to inhibit neovascularisation and are therefore used successfully in tumour therapy.

Diminishing the side effect of mitomycin C by using pH-sensitive liposomes: in vitro characterization and in vivo pharmacokinetics

“…In clinical settings, more than 80% of all cancers are solid tumors. 9 Based on tumor pathophysiology, there is a pH gradient between the extracellular pH (pHe 7.2) and intracellular pH (pHi 5.7–7.8), which exists as a gradient gap. By contrast, normal tissue maintains a constant pH of 7.4, and the pHi remains at 7.2.…”

Cancer Immunotherapy Confers a Global Benefit

“…These mAbs are now underway for a wide range of cancers from hematological malignancies to solid tumors, but these have not yet entered into clinical trials [ 211 , 212 ]. Of note that, mAbs act as immunomodulators, trigger complement activation, induce Antibodydependent cell-mediated cytotoxicity (ADCC) and also are able to provide opportunity for targeted delivery of cytotoxic materials to malignant cells (for instance 131 I-tositumomab, known as radioimmunotherapy) [ 213 ]. Figure 1.12 summarizes immunotherapies aimed at stimulating antitumor immune responses.…”

For Breast Cancer Prognosis, Immunoglobulin Kappa Chain Surfaces to the Top

“…These tumor antigen– specific antibodies are capable of amplifying innate and adaptive cellular immune responses to the detriment of the tumor and, thus, are likely to benefit the patient. The efficacy of cancer immunotherapies with tumor antigen– specific antibodies, such as rituximab, cetuximab, and trastuzumab, is thought to be mediated via antibody-dependent cellular cytotoxicity and/or the inhibition of major signaling pathways (2, 7). These mechanisms may be responsible in part for the current findings identifying IGKC as a robust marker of better prognosis and response to chemotherapy.…”