PMN and anti-tumor immunity—The case of bladder cancer immunotherapy

Brincks, Erik L.; Risk, Michael; Griffith, Thomas S.

doi:10.1016/j.semcancer.2013.02.002

Cited by 40 publications

(31 citation statements)

References 102 publications

(101 reference statements)

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“…The majority of these patients present with superficial transitional cell carcinoma (Tis, Ta, or T1) that is treated with transurethral resection followed by intravesical chemotherapy, or for high-risk tumors local Bacillus Calmette-Guerin (BCG) immunotherapy (2,3). BCG treatment induces remission in a majority of patients but is associated with adverse events and 30% to 50% of the patients ultimately fail to respond (4).…”

Section: Introductionmentioning

confidence: 99%

Locally Delivered CD40 Agonist Antibody Accumulates in Secondary Lymphoid Organs and Eradicates Experimental Disseminated Bladder Cancer

Sandin

Orlova

Gustafsson

et al. 2014

Cancer Immunology Research

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Immunotherapy with intratumoral injection of adenoviral vectors expressing CD40L has yielded positive results in experimental and clinical bladder cancer. We therefore hypothesized that anti-CD40 antibody would be effective in this setting. Agonistic CD40 antibodies were developed as vaccine adjuvants but have later been used as treatment of advanced solid tumors and hematologic cancers. Systemic anti-CD40 therapy has been associated with immune-related adverse events, such as cytokine release syndrome and liver toxicity, and local delivery is an attractive approach that could reduce toxicity. Herein, we compared local and systemic anti-CD40 antibody delivery to evaluate efficacy, toxicity, and biodistribution in the experimental MB49 bladder cancer model. Antitumor effects were confirmed in the B16 model. In terms of antitumor efficacy, local anti-CD40 antibody stimulation was superior to systemic therapy at an equivalent dose and CD8 T cells were crucial for tumor growth inhibition. Both administration routes were dependent on host CD40 expression for therapeutic efficacy. In vivo biodistribution studies revealed CD40-specific antibody accumulation in the tumor-draining lymph nodes and the spleen, most likely reflecting organs with frequent target antigen-expressing immune cells. Systemic administration led to higher antibody concentrations in the liver and blood compared with local delivery, and was associated with elevated levels of serum haptoglobin. Despite the lack of a slow-release system, local anti-CD40 therapy was dependent on tumor antigen at the injection site for clearance of distant tumors. To summarize, local low-dose administration of anti-CD40 antibody mediates antitumor effects in murine models with reduced toxicity and may represent an attractive treatment alternative in the clinic. Cancer Immunol Res; 2(1); 80-90. Ó2013 AACR.

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Section: Introductionmentioning

confidence: 99%

Locally Delivered CD40 Agonist Antibody Accumulates in Secondary Lymphoid Organs and Eradicates Experimental Disseminated Bladder Cancer

Sandin

Orlova

Gustafsson

et al. 2014

Cancer Immunology Research

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“…13 Further, granulocytes are important anti-cancer immune effector cells in carcinoma, lymphoma and melanoma, 14,15 and are required for clinical activity of bladder cancer immunotherapy. 16 The most important function of granulocytes is that of phagocytosis of target cells. To a far lesser extent, granulocytes C, 4 C, and 37 C, after which CLL1-restricted activity was analyzed on the Ramos.CLL-1/Ramos cell line pair.…”

Section: Discussionmentioning

confidence: 99%

C-type lectin-like molecule-1 (CLL1)-targeted TRAIL augments the tumoricidal activity of granulocytes and potentiates therapeutic antibody-dependent cell-mediated cytotoxicity

Wiersma

Bruyn

Shi

et al. 2015

mAbs

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“…In an mouse model assay, these author showed increased production of IFN-γ and GMCSF by splenocytes, decreased production of IL-10, elevated cellular proliferation, and higher differentiation of IFN-γ-secreting cells (Luo et al 2004). Since that IL-10 has been associated with inhibition of BCG-mediated macrophage cytotoxicity against bladder cancer cells (Luo 2012;Sun et al 2010) and IFN-γ is one of the major Th1-stimulating cytokine (Brincks et al 2013), these results suggest that rBCG-IL2 or rBCG-IL18 augment BCG's immunostimulatory response and anticancer property.…”

Section: Rbcg Expressing Cytokinesmentioning

confidence: 96%

“…IFNs are a soluble class of cytokines produced for several types of immune cells in response to pathogens like virus and bacteria. In bladder cancer, IFNs plays a key role in the development of an immune response against tumor cells after BCG instillation and it is one of the cytokines responsible for stimulation of sTRAIL production and release in PMN cells (Brincks et al 2013). Several studies have generated IFNs-secreting BCG strains as a possible alternative to bladder cancer treatment.…”

Section: Rbcg Expressing Cytokinesmentioning

confidence: 99%

Recombinant Mycobacterium bovis BCG for immunotherapy in nonmuscle invasive bladder cancer

Begnini

Buss

Collares

et al. 2015

Appl Microbiol Biotechnol

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In the past three decades, intravesical instillation of Mycobacterium bovis bacille Calmette-Guérin (BCG) has been used for treating bladder cancer and it still remains at the forefront of immunotherapy for cancer patients. Although BCG-based therapy is the most effective intravesical therapy for this kind of tumor and represents the only agent known to reduce progression into muscle invasive bladder cancer, BCG is ineffective in approximately 30-40 % of cases and disease recurs in up to 50 % of patients. Since that BCG is considered an effective vehicle for delivery of antigens due to its unique characteristics, the genetic manipulation of these mycobacteria has been appealing in the search for less toxic and more potent therapeutic agents for bladder cancer immunotherapy. Herein, we discuss current advances in recombinant BCG construction, research, concerns, and future directions to promote the development of this promising immunotherapeutic approach for bladder cancer.

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PMN and anti-tumor immunity—The case of bladder cancer immunotherapy

Cited by 40 publications

References 102 publications

Locally Delivered CD40 Agonist Antibody Accumulates in Secondary Lymphoid Organs and Eradicates Experimental Disseminated Bladder Cancer

Locally Delivered CD40 Agonist Antibody Accumulates in Secondary Lymphoid Organs and Eradicates Experimental Disseminated Bladder Cancer

C-type lectin-like molecule-1 (CLL1)-targeted TRAIL augments the tumoricidal activity of granulocytes and potentiates therapeutic antibody-dependent cell-mediated cytotoxicity

Recombinant Mycobacterium bovis BCG for immunotherapy in nonmuscle invasive bladder cancer

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