Clinical Update: Treatment of Glioblastoma Multiforme with Radiolabeled Antibodies that Target Tumor Necrosis

Jensen, Randy L.; Shan, Joseph; Freimark, Bruce; Harris, Debra A.; King, Steven W.; Lai, Jennifer C.; Parseghian, Missag H.

doi:10.2174/157339410790596489

Cited by 2 publications

(2 citation statements)

References 32 publications

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“…Taking a cue from these studies, Luhrs et al (2009) investigated a modified purification scheme for a histone H1/DNA binding antibody already in clinical trials for the treatment of stage IV brain tumors. Given the tradename Cotara ® , it has already been tested in 100 patients suffering from glioblastoma multiforme with some remarkable success (Jensen et al 2010). The antibody is manufactured by mammalian cells in a bioreactor, where the increasing number of dead cells and debris can lead to hitchhiker contamination by the end of the fermentation.…”

Section: The Impact Of Hitchhiker Contamination On Medicinementioning

confidence: 99%

Hitchhiker antigens: Inconsistent ChIP results, questionable immunohistology data, and poor antibody performance may have a common factor

Parseghian

2013

Biochem. Cell Biol.

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Questionable data and poor antibody performance may have a common factor: antigens "hitchhiking" on the very antibodies designed to target them. Here I focus on histone hitchhikers and their antibodies, given the impact of chromatin immunoprecipitation on our understanding of DNA regulation. Caused by a lack of stringency during antibody purification, hitchhikers will impede important advances in chromatin research and therapeutics derived from that research, if similar circumstances in the study of lupus decades ago are any guide. Evidence of this phenomenon is reviewed, purification modifications for antibody manufacturing are suggested, and a histone hitchhiker detection procedure is provided.

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Section: The Impact Of Hitchhiker Contamination On Medicinementioning

confidence: 99%

Hitchhiker antigens: Inconsistent ChIP results, questionable immunohistology data, and poor antibody performance may have a common factor

Parseghian

2013

Biochem. Cell Biol.

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“…Therefore, alternative strategies involve local immune manipulation by local administration of immune activating agents in combination with local destruction of tumor tissue, and associated liberation of TAAs following surgical ablation or tumor targeting by “magic bullets” such as TAA-specific or tumor cell DNA-targeting antibodies. Examples include the radiotherapeutic strategy, called Cotara ® , that employs the isotope 131 Iodine conjugated to an antibody that binds the necrotic core found in all solid tumors [62], or antibody-targeted delivery of chemokines by chemokine/antibody fusion proteins, which results in high local tumor-associated concentrations of chemokines that attract monocytes, neutrophils and lymphocytes [63]. Yet another variant of this concept includes locoregional or intratumor application of oncolytic viruses, e.g.…”

Section: Key Considerations For Development Of Immunotherapy Approachesmentioning

confidence: 99%

Immunotherapy of Malignant Gliomas Using Autologous and Allogeneic Tissue Cells

Hofman¹,

Stathopoulos²,

Kruse³

et al. 2010

ACAMC

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Immunotherapy of brain tumors is rapidly emerging as a potential clinical option [1–3]. The quality and magnitude of immune responses evoked by the new generation anti-tumor vaccines is in general highly dependent on the source or choice of peptide antigens, and as well, a suitable immunopotentiator. Poorly immunogenic antigens, such as those present in tumor cell lysates, may not reliably provide stimulation like recombinant or DNA-encoded protein antigens might be expected to. In addition, the efficacy of the vaccine may depend on inherent counteracting measures of the tumor which dampen immune surveillance and immune effector activity triggered by immunization [4]. Our body has many means of limiting an immune response to our own (self) proteins. In particular, patients with gliomas exhibit a broad suppression of cell-mediated immunity [5–8]. Unfortunately, for most tumor vaccines the induction of local or systemic immune effector cells does not necessarily translate into objective clinical responses or increased survival [9]. Here we review immunotherapeutic approaches against gliomas and recent pre-clinical and clinical initiatives based on cellular or active immunization of the patient’s immune system using autologous and allogeneic tissues or cultured cells. Available evidence shows that single modality cancer therapies likely remain suboptimal. Combination regimens targeting the immune system at multiple coordinated levels must be developed, and possibly combined with strategies to inhibit immune suppressive factors if significant clinical benefit is to be achieved.

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Clinical Update: Treatment of Glioblastoma Multiforme with Radiolabeled Antibodies that Target Tumor Necrosis

Cited by 2 publications

References 32 publications

Hitchhiker antigens: Inconsistent ChIP results, questionable immunohistology data, and poor antibody performance may have a common factor

Hitchhiker antigens: Inconsistent ChIP results, questionable immunohistology data, and poor antibody performance may have a common factor

Immunotherapy of Malignant Gliomas Using Autologous and Allogeneic Tissue Cells

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