Combining Adoptive Cellular and Immunocytokine Therapies to Improve Treatment of B-Lineage Malignancy

Singh, Harjeet; Serrano, Lisa Marie; Pfeiffer, Timothy; Olivares, Simon; McNamara, George; Smith, David; Al-Kadhimi, Zaid; Forman, Stephen J.; Gillies, Stephen D.; Jensen, Michael C.; Colcher, David; Raubitschek, Andrew; Cooper, Laurence J.N.

doi:10.1158/0008-5472.can-06-2283

Cited by 37 publications

(28 citation statements)

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“…33,34 We reported that adoptively transferred T cells infiltrated pulmonary tumor nodules and eradicated established tumor metastases. 35 Using MHC class I-restricted TCR transgenic T cells from the OT-1 mouse, which are specific for the surrogate tumor Ag ovalbumin, our group also found that exogenous IL-2 promoted T-cell persistence after adoptive transfer, and donor CD8 þ T cells developed a memory phenotype based on CD44 and Ly6c expression.…”

Section: Discussionmentioning

confidence: 99%

Genetically engineered T cells expressing a HER2-specific chimeric receptor mediate antigen-specific tumor regression

Yang

Urban

et al. 2008

Cancer Gene Ther

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In this report, we developed a chimeric receptor (N29g chR) involving the single chain Fv (scFv) derived from N29 monoclonal antibody (mAb) specific for p185HER2 and characterized the therapeutic efficacy of primary T cells engineered to express N29g chR in two histologically distinct murine tumor models. Murine breast (MT901) and fibrosarcoma (MCA207) cancer cell lines were engineered to express human HER2 as targets. Administration of N29g chR-expressing T cells eliminated 3-day pulmonary micrometastases of MT901/HER2 and MCA207/HER2 but not parental tumor cells. A 5 to 8-fold increased dose of N29g T cells was required to mediate regression of advanced 8-day macrometastases. Exogenous administration of interleukin-2 (IL-2) after N29g T-cell transfer was dispensable for treatment of 3-day micrometastases, but was required for mediating regression of wellestablished 8-day macrometastases. Moreover, fractionated CD8 T cells expressing N29g chR suppressed HER2-positive tumor cell growth after adoptive transfer independent of CD4 þ cells. These data indicate that genetically modified T cells expressing a HER2-targeting chimeric receptor can mediate antigen-specific regression of preestablished metastatic cancers in a cell dose-dependent fashion. Systemic administration of IL-2 augments the therapeutic efficacy of these genetically engineered T cells in advanced diseases. These results are relevant to the implication of genetically redirected T cells in clinical cancer immunotherapy.

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Section: Discussionmentioning

confidence: 99%

Genetically engineered T cells expressing a HER2-specific chimeric receptor mediate antigen-specific tumor regression

Yang

Urban

et al. 2008

Cancer Gene Ther

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“…97 Antibodies fused to a cellsignaling molecule (immunocytokines) comprise another increasingly recognized group of ICs with activity in hematologic malignancies. 98 A tetrameric interferon-a construct attached to veltuzumab showed promising activity in a lymphoma mouse xenograft model. 99 Drug and linker affect the efficacy and toxicity profile of ADCs.…”

Section: Adcsmentioning

confidence: 99%

Advances in the treatment of hematologic malignancies using immunoconjugates

Palanca-Wessels

Press

2014

Blood

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Monoclonal antibody therapy has revolutionized cancer treatment by significantly improving patient survival both in solid tumors and hematologic malignancies. Recent technological advances have increased the effectiveness of immunotherapy leading to its broader application in diverse treatment settings. Immunoconjugates (ICs) consist of a cytotoxic effector covalently linked to a monoclonal antibody that enables the targeted delivery of its therapeutic payload to tumors based on cell-surface receptor recognition. ICs are classified into 3 groups based on their effector type: immunotoxins (protein toxin), radioimmunoconjugates (radionuclide), and antibody drug conjugates (small-molecule drug). Optimization of each individual component of an IC (antibody, linker, and effector) is essential for therapeutic efficacy. Clinical trials have been conducted to investigate the effectiveness of ICs in hematologic malignancies both as monotherapy and in multiagent regimens in relapsed/refractory disease as well as frontline settings. These studies have yielded encouraging results particularly in lymphoma. ICs comprise an exciting group of therapeutics that promise to play an increasingly important role in the management of hematologic malignancies.

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“…(57,272,281) The CAR was modified to replace CD28 endodomain for CD137 endodomain as a synthetic cDNA sequence Identities of final ROR1R plasmids were distinguished from CD19R plamids by PmlI enzyme and pSBSO-SIM and pSBSO-FRA plasmids were distinguished by BsrGI enzyme (Figure 7).…”

Section: Via3 Chimeric Antigen Receptorsmentioning

confidence: 99%

Innovative T Cell-Targeted Therapy for Ovarian Cancer

Cooper¹

2014

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Combining Adoptive Cellular and Immunocytokine Therapies to Improve Treatment of B-Lineage Malignancy

Cited by 37 publications

References 50 publications

Genetically engineered T cells expressing a HER2-specific chimeric receptor mediate antigen-specific tumor regression

Genetically engineered T cells expressing a HER2-specific chimeric receptor mediate antigen-specific tumor regression

Advances in the treatment of hematologic malignancies using immunoconjugates

Innovative T Cell-Targeted Therapy for Ovarian Cancer

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