NK cell depletion results in accelerated tumor growth and attenuates the antitumor effect of total body irradiation

Miller, Glen M.; Andres, Melba L.; Gridley, Daila S.

doi:10.3892/ijo.23.6.1585

Cited by 12 publications

(10 citation statements)

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“…The murine monoclonal IgG 3 antibody JAA-F11 [24] is highly specific in that it binds to the alpha-linked tumor-associated TF-Ag and not the beta-linked structure known to be localized on the surface of normal tissues such as the kidney and natural killer (NK) cells [25] , [26] , [27] . The in vivo specificity of JAA-F11 was observed using iodine 124-labeled JAA-F11 in the mouse 4T1 breast cancer model, the nude-xenograft human breast cancer model (MDA-MB-231(triple negative)) and the SCID-xenograft human breast cancer model (with DU4475 triple negative tumors) [27] , [28] , [29] .…”

Section: Introductionmentioning

confidence: 99%

Humanization of JAA-F11, a Highly Specific Anti-Thomsen-Friedenreich Pancarcinoma Antibody and In Vitro Efficacy Analysis

et al. 2017

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JAA-F11 is a highly specific mouse monoclonal to the Thomsen-Friedenreich Antigen (TF-Ag) which is an alpha-O-linked disaccharide antigen on the surface of ~80% of human carcinomas, including breast, lung, colon, bladder, ovarian, and prostate cancers, and is cryptic on normal cells. JAA-F11 has potential, when humanized, for cancer immunotherapy for multiple cancer types. Humanization of JAA-F11, was performed utilizing complementarity determining regions grafting on a homology framework. The objective herein is to test the specificity, affinity and biology efficacy of the humanized JAA-F11 (hJAA-F11). Using a 609 target glycan array, 2 hJAA-F11 constructs were shown to have excellent chemical specificity, binding only to TF-Ag alpha-linked structures and not to TF-Ag beta-linked structures. The relative affinity of these hJAA-F11 constructs for TF-Ag was improved over the mouse antibody, while T20 scoring predicted low clinical immunogenicity. The hJAA-F11 constructs produced antibody-dependent cellular cytotoxicity in breast and lung tumor lines shown to express TF-Ag by flow cytometry. Internalization of hJAA-F11 into cancer cells was also shown using a surface binding ELISA and confirmed by immunofluorescence microscopy. Both the naked hJAA-F11 and a maytansine-conjugated antibody (hJAA-F11-DM1) suppressed in vivo tumor progression in a human breast cancer xenograft model in SCID mice. Together, our results support the conclusion that the humanized antibody to the TF-Ag has potential as an adjunct therapy, either directly or as part of an antibody drug conjugate, to treat breast cancer, including triple negative breast cancer which currently has no targeted therapy, as well as lung cancer.

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Section: Introductionmentioning

confidence: 99%

Humanization of JAA-F11, a Highly Specific Anti-Thomsen-Friedenreich Pancarcinoma Antibody and In Vitro Efficacy Analysis

et al. 2017

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“…In addition TF-Ag can be modulated by sulfation [97,98]. The closely related Galβ1–3GalNAc β is present in glycolipids of the spleen white and red pulp [99], kidney tubules [100,101], regenerating respiratory epithelial cells [100], and NK cells [102,103]. Therefore, the vaccine response must be specific in order for this antigen to be targeted.…”

Section: The Mucin Related Tumor-associated Antigensmentioning

confidence: 99%

Cancer vaccines and carbohydrate epitopes

Heimburg-Molinaro

Lum

Vijay

et al. 2011

Vaccine

217

152

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Tumor-associated carbohydrate antigens (TACA) result from the aberrant glycosylation that is seen with transformation to a tumor cell. The carbohydrate antigens that have been found to be tumor-associated include the mucin related Tn, Sialyl Tn, and Thomsen-Friedenreich antigens, the blood group Lewis related LewisY, Sialyl LewisX and Sialyl LewisA, and LewisX, (also known as stage-specific embryonic antigen-1, SSEA-1), the glycosphingolipids Globo H and stage-specific embryonic antigen-3 (SSEA-3), the sialic acid containing glycosphingolipids, the gangliosides GD2, GD3, GM2, fucosyl GM1, and Neu5GcGM3, and polysialic acid. Recent developments have furthered our understanding of the T-independent type II response that is seen in response to carbohydrate antigens. The selection of a vaccine target antigen is based on not only the presence of the antigen in a variety of tumor tissues but also on the role this antigen plays in tumor growth and metastasis. These roles for TACAs are being elucidated. Newly acquired knowledge in understanding the T-independent immune response and in understanding the key roles that carbohydrates play in metastasis are being applied in attempts to develop an effective vaccine response to TACAs. The role of each of the above mentioned carbohydrate antigens in cancer growth and metastasis and vaccine attempts using these antigens will be described.

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“…NK cells represent the first line of defence against virus-infected and neoplastic cells and initiate cell lysis and cytokine production in the absence of prior antigenic stimulation [1,2,4]. The potential role of NK cells in the control of cancer has been suggested by the observation of an inverse correlation between the NK cell count and incidence of malignant disease in cohort studies of humans with further support derived from murine studies [5-7]. NK cell participation has been reported in the immune response to several viruses including HIV, hepatitis B and C, but it may have particular relevance in host defence against herpes viridae [7-9].…”

Section: Introductionmentioning

confidence: 99%

Ageing is associated with a decline in peripheral blood CD56bright NK cells

et al. 2006

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Background: Natural killer (NK) cells are cytotoxic lymphocytes that lack CD3 and express variable levels of CD16, CD56 and CD57. In recent years NK cells have been categorised into two major groups based on the level of CD56 expression. This phenotypic classification correlates with functional activity as CD56 bright NK cells are the major cytokine producing subset whereas CD56 dim NK cells exhibit greater cytotoxic activity. Previous studies have revealed a reduction in total NK cell numbers in association with ageing and this study sought to determine the potential influence of ageing on the number of NK cell subsets within peripheral blood.

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NK cell depletion results in accelerated tumor growth and attenuates the antitumor effect of total body irradiation

Cited by 12 publications

References 0 publications

Humanization of JAA-F11, a Highly Specific Anti-Thomsen-Friedenreich Pancarcinoma Antibody and In Vitro Efficacy Analysis

Humanization of JAA-F11, a Highly Specific Anti-Thomsen-Friedenreich Pancarcinoma Antibody and In Vitro Efficacy Analysis

Cancer vaccines and carbohydrate epitopes

Ageing is associated with a decline in peripheral blood CD56bright NK cells

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