Keyhole Limpet Hemocyanine Can Enhance the Natural Killer Activity of Patients with Transitional Cell Carcinoma of the Bladder

Moltó, Luis; Carballido, J; Jurincic, C.; Lapeña, P; Manzano, L; Salmerón, I; Klippel, K. F.; Álvarez‐Mon, Melchor

doi:10.1159/000473584

Cited by 11 publications

(6 citation statements)

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“…It has been reported that MBT-2 cells do not grow when they are injected into the bladders of mice treated with a combination of IL-2 and the cytotoxic agent cyclophosphamide (Ikemoto et al, 1997). Moreover, KLH has been shown to enhance NK cell activity and stimulate IFN- secretion in SBC patients (Molto et al, 1991). Our later results confirm these observations; mice treated with KLH or CCH increase NK cell activity and serum levels of IFN- (Moltedo et al, 2006).…”

Section: Patientssupporting

confidence: 83%

Hemocyanins in the Immunotherapy of Superficial Bladder Cancer

Arancibia¹,

Salazar²,

Becker³

2012

Bladder Cancer - From Basic Science to Robotic Surgery

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Section: Patientssupporting

confidence: 83%

Hemocyanins in the Immunotherapy of Superficial Bladder Cancer

Arancibia¹,

Salazar²,

Becker³

2012

Bladder Cancer - From Basic Science to Robotic Surgery

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“…Second, hemocyanins are slowly processed [25], and third, hemocyanins stimulate T-helper cell responses, supporting the secretion of cytokines such as IFN-γ and IL-2 by tumor reactive T cells localized in the regional lymph nodes [11]. This inflammatory environment enhances NK cell activity in patients with superficial bladder cancer [57] and in mouse models of this cancer [20], and it is known that NK cells are strongly stimulated by IL-2 to differentiate into lymphokine-activated killer cells [58]. Finally, NK cells can delay tumor growth by means of antibody-dependent cell-mediated cytotoxicity of effector cells [59].…”

Section: Discussionmentioning

confidence: 99%

A Novel Immunomodulatory Hemocyanin from the Limpet Fissurella latimarginata Promotes Potent Anti-Tumor Activity in Melanoma

et al. 2014

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Hemocyanins, the huge oxygen-transporting glycoproteins of some mollusks, are used as immunomodulatory proteins with proven anti-cancer properties. The biodiversity of hemocyanins has promoted interest in identifying new anti-cancer candidates with improved immunological properties. Hemocyanins promote Th1 responses without known side effects, which make them ideal for long-term sustained treatment of cancer. In this study, we evaluated a novel hemocyanin from the limpet/gastropod Fissurella latimarginata (FLH). This protein has the typical hollow, cylindrical structure of other known hemocyanins, such as the keyhole limpet hemocyanin (KLH) and the Concholepas hemocyanin (CCH). FLH, like the KLH isoforms, is composed of a single type of polypeptide with exposed N- and O-linked oligosaccharides. However, its immunogenicity was significantly greater than that of KLH and CCH, as FLH induced a stronger humoral immune response and had more potent anti-tumor activity, delaying tumor growth and increasing the survival of mice challenged with B16F10 melanoma cells, in prophylactic and therapeutic settings. Additionally, FLH-treated mice demonstrated increased IFN-γ production and higher numbers of tumor-infiltrating CD4+ lymphocytes. Furthermore, in vitro assays demonstrated that FLH, but not CCH or KLH, stimulated the rapid production of pro-inflammatory cytokines (IL-6, IL-12, IL-23 and TNF-α) by dendritic cells, triggering a pro-inflammatory milieu that may explain its enhanced immunological activity. Moreover, this effect was abolished when deglycosylated FLH was used, suggesting that carbohydrates play a crucial role in the innate immune recognition of this protein. Altogether, our data demonstrate that FLH possesses increased anti-tumor activity in part because it activates a more potent innate immune response in comparison to other known hemocyanins. In conclusion, FLH is a potential new marine adjuvant for immunization and possible cancer immunotherapy.

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“…by induction of IL-2 [35], activation of macrophages [36] and cytotoxic T lymphocytes [37], as well as by direct inhibition of tumor cells [38]. In conjunc tion with IL-2 and interferon-y it induces NK-cell-dependent tumor cell destruction [39], We have recently shown that KLH modulates the cytotoxic activity of NK cells [9], The data suggest that responsing patients (i.e. those who remained tumor free after therapy) produced higher levels of IL-la than non-responders but the levels failed to reach statistical significance.…”

Section: Discussionmentioning

confidence: 99%

“…This stimulato ry effect has been involved in the induction of effector lymphocytes against neoplastic cells [9], Klippel et al [10] demonstrated this by locally injecting KLH into the blad der thereby inducing a mononuclear cell infiltration. We have recently shown that the intravesical instillation of KLH into patients with superficial transitional cell carci noma (TCC) is also associated with marked lymphocyte and macrophage infiltration of the bladder mucosa and submucosa [11,12].…”

Section: Introductionmentioning

confidence: 99%