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Bi-specific and tri-specific antibodies- the next big thing in solid tumor therapeutics.

ABSTRACT: Antibody-based therapy has revitalized the world of cancer therapeutics since rituximab was first approved for the treatment of Non-Hodgkin's Lymphoma. Monoclonal antibodies against cancer antigens have been successful strategies for only a handful of cancer types due to many reasons including lack of antibody specificity and complex nature of tumor milieu which interfere with antibody efficacy. Polyspecific antibodies are promising class of anti-cancer agents which can be directed at multiple tumor antigens to eradicate tumor cells more precisely and effectively. They may overcome some of these limitations and have already changed treatment landscape for some malignancies such as B cell acute lymphoblastic leukemia. Pre-clinical studies and early phase clinical trials have demonstrated that this approach may be an effective strategy even for solid tumors. This review focuses on the development of bispecific and trispecific antibody therapy for the treatment of solid tumor malignancies and highlights the potential they hold for future therapies to come.

SUBMITTER: Runcie K

PROVIDER: S-EPMC6154901 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Bi-specific and tri-specific antibodies- the next big thing in solid tumor therapeutics.

Runcie Karie K Budman Daniel R DR John Veena V Seetharamu Nagashree N

Molecular medicine (Cambridge, Mass.) 20180924 1

Antibody-based therapy has revitalized the world of cancer therapeutics since rituximab was first approved for the treatment of Non-Hodgkin's Lymphoma. Monoclonal antibodies against cancer antigens have been successful strategies for only a handful of cancer types due to many reasons including lack of antibody specificity and complex nature of tumor milieu which interfere with antibody efficacy. Polyspecific antibodies are promising class of anti-cancer agents which can be directed at multiple t ...[more]

PMID: 30249178

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Project description:PURPOSE:To compare diffusion tensor imaging (DTI), intravoxel incoherent motion (IVIM), and tri-exponential models of the diffusion magnetic resonance imaging (MRI) signal for the characterization of renal lesions in relationship to histopathological findings. METHODS:Sixteen patients planned to undergo nephrectomy for kidney tumour were scanned before surgery at 3?T magnetic resonance imaging (MRI), with T2-weighted imaging, DTI and diffusion weighted imaging (DWI) using ten b-values. DTI parameters (mean diffusivity [MD] and fractional anisotropy [FA]) were obtained by iterative weighted linear least squared fitting of the DTI data and bi-, and tri-exponential fit parameters (Dbi, fstar,and Dtri, ffast,finterm) using a nonlinear fit of the multiple b-value DWI data. Average parameters were calculated for regions of interest, selecting the lesions and healthy kidney tissue. Tumour type and specificities were determined after surgery by histological examination. Mean parameter values of healthy tissue and solid lesions were compared using a Wilcoxon-signed ranked test and MANOVA. RESULTS:Thirteen solid lesions (nine clear cell carcinomas, two papillary renal cell carcinoma, one haemangioma and one oncocytoma) and four cysts were included. The mean MD of solid lesions are significantly (p?<?0.05) lower than healthy cortex and medulla, (1.94?±?0.32*10-?3?mm2/s versus 2.16?±?0.12*10-?3?mm2/s and 2.21?±?0.14*10-?3?mm2/s, respectively) whereas ffast is significantly higher (7.30?±?3.29% versus 4.14?±?1.92% and 4.57?±?1.74%) and finterm is significantly lower (18.7?±?5.02% versus 28.8?±?5.09% and 26.4?±?6.65%). Diffusion coefficients were high (?2.0*10-?3?mm2/s for MD, 1.90*10-?3?mm2/s for Dbi and 1.6*10-?3?mm2/s for Dtri) in cc-RCCs with cystic structures and/or haemorrhaging and low (?1.80*10-?3?mm2/s for MD, 1.40*10-?3?mm2/s for Dbi and 1.05*10-?3?mm2/s for Dtri) in tumours with necrosis or sarcomatoid differentiation. CONCLUSION:Parameters derived from a two- or three-component fit of the diffusion signal are sensitive to histopathological features of kidney lesions.

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Bi-specific and tri-specific antibodies- the next big thing in solid tumor therapeutics.

Publications

Bi-specific and tri-specific antibodies- the next big thing in solid tumor therapeutics.

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