The larger size of the antibodies minimizes the unwanted diffusion through plasma-membrane associated with small molecules playing a crucial role in specific targeting of the biomolecules avoiding the side effects [16,39,47]. resistance against these antibodies, combination therapy is thought to be the best bet for patient care. Here, in this review, we have discussed different aspects of antibodies in cancer therapy affecting their efficacy and mechanism of resistance with some relevant examples of the most studied molecules approved by the US FDA. Keywords:Antibody, Cancer therapy, Antibodydrug conjugate (ADC), Immune-modulation, Chemo-resistance == Introduction == Cancer is the second leading cause of death worldwide and claims approximately one out of six deaths. The heterogeneity in cancer with complex and immuno-suppressive tumor microenvironment is the real challenge to treat the disease. Acquired therapeutic resistance and the process of metastasis further aggravates the outcome due to poor prognosis and so accounts for major cause of cancer related deaths [18]. Despite our growing understanding of the disease, the worldwide diagnosed new cases and PLpro inhibitor deaths are expected to increase in the future. For 2018, International agency for Research on cancer (IARC), estimated 18.0 million new cases and 9.5 million deaths worldwide (Fig.1). Nonetheless, this number is expected to increase gradually up to 27.5 million new cases and 16.3 million deaths in year 2040. == Fig. 1. == Estimated number of cancer new cases and death in 2018 by World Health Organization (WHO). For 2018, the estimated number of new cancer cases PLpro inhibitor and death due to the malignancy in the world was 18 and 9.5 million respectively Treatment of cancer mostly involves combination of surgery with chemo or radiation therapy. To control the side effects of conventional systemic chemotherapy, targeting molecules are prescribed to block cell proliferation and/or modulate immune response of patients having significant impact on our existing therapeutics in cancer care. Monoclonal antibodies (mAbs) are very important entities out there in the p45 market along with small molecule inhibitors (SMIs) for targeted therapy of cancer, the former with a better specificity coupled with biological activity. The larger size of the antibodies minimizes the unwanted diffusion through plasma-membrane associated with small molecules playing a crucial role in specific targeting of the biomolecules avoiding the side effects [16,39,47]. The global monoclonal antibody therapeutics market was estimated at $100B USD in 2017 which is expected to reach around $219B USD by 2023 growing at a CAGR of around 12.5% during 2017 to 2023 (Zion market research). Paul Ehrlichs concept of magic bullet, originated back in nineteenth century, inspired many others leading to the discovery of antibodys ability to recognize the target antigen on the cell surface without harming the individual. The effort of using antibody for cancer treatment started with immunization of animals but the attempt to get anti-sera with some degree of cancer specificity could not get much success [45]. The development of inbred mice and cytotoxic assay for cell surface reactivity of alloantibodies contributed in better understanding of cell surface differentiation antigens leading to distinction between normal and malignant cells. Later, development of hybridoma technology discovered by Kohler and Milstein in 1975 met the success with analytical tools such as fluorescence-activated cell sorting (FACS) [29,40]. The term hybridoma was suggested by Leonard Herzenberg for combining immortalization of the myeloma cells with development of selection techniques for antibody producing B cells; the two important inventions together. For the first time, antigen specific monoclonal antibodies could be developed from immortalized B lymphocytes of immunized mice spleen. The technology proved to be a weapon in dissecting the surface proteins of malignant versus healthy cells leading to greater insight into tumorigenesis [41]. But these mice monoclonal antibodies were not of much use for cancer patients because of the immunological response generating human PLpro inhibitor anti-mouse antibody (HAMA) when injected in human resulting in rapid PLpro inhibitor inactivation and clearance from patient serum. This also restricted multiple administration of the murine antibody required for the treatment. The advancement in recombinant technology empowered our scientists to produce chimeric, humanized, and human antibodies (Fig.2) that geared up our fight against cancer and the current list of the FDA approved monoclonal antibodies reflects the revolution in patient care (Table1). == Fig. 2. == Transition of Monoclonal antibody from mouse to human.Murine: These antibodies originate in mice and so are mice proteins. The names of these molecules end PLpro inhibitor in -omab.Chimeric: These are engineered antibodies in which constant regions of both chains are of human origin; however, the variable domain origin is different but not synthesized. The names of the modality end in -ximab.Humanized: These engineered molecules have everything of human origin except CDR regions of variable domain of both the chains that might be synthesized one too. The names of the treatments end in zumab.Human: These are fully human proteins and the names of the molecules end in -umab == Table 1. == FDA approved antibodies for cancer treatment B-cell NHL CLL 1997 2010 Ibritumomab Tiuxetan.