Natural killer (NK) cells lead immune surveillance against cancer and early elimination of small tumors. Owing to their ability to engage tumor targets without the need of specific antigen, the therapeutic potential of NK cells has been extensively explored in hematological malignancies. In solid tumors, however, their role in the clinical arena remains poorly exploited despite a broad accumulation of preclinical data. In this article, we review our current knowledge of NK cells’ biology, and highlight the challenges facing NK cell antitumor strategies in solid tumors. We further summarize the abundant preclinical attempts at overcoming these challenges, present past and ongoing clinical trial data and finally discuss the potential impact of novel insights on the development of NK cell-based therapies.
With growing use of nivolumab, rare but serious side effects have surfaced in some patients. We present a case of autoimmune haemolytic anaemia that developed after 39 cycles of nivolumab. A 78-year-old man with metastatic lung adenocarcinoma, refractory to multiple lines of chemotherapy was switched to nivolumab. After around 2 years of stable course on nivolumab, he developed transfusion-dependent anaemia with haemoglobin of 8.6 g/dL. Nivolumab was held immediately. Bone marrow biopsy findings were inconclusive of myelodysplastic syndrome. Further testing was suggestive of haemolysis with haptoglobin <10 mg/dL, elevated reticulocyte count and identification of immunoglobulin G antibody. Haemoglobin improved significantly with initiation of 1 mg/kg prednisone in addition to rituximab weekly × four doses. The development of transfusion-dependent anaemia with the exposure to cytotoxic chemotherapy usually raises the question for myelodysplastic syndrome. In contradiction, our patient was diagnosed to have a haematological autoimmune complication related to immunotherapy.
HighlightsNext-generation sequencing can identify and offer new treatment options.Demonstration of the successful use of targeted therapy in metastatic cervical cancer.Patient sequentially responded to trastuzumab-pertuzumab followed by TDM-1.Duration of therapy has been four years and she continues to respond.
Ibrutinib has revolutionized the treatment of B-cell malignancies since its approval for chronic lymphocytic leukemia. It is also used in mantle cell lymphoma, diffuse large B-cell lymphoma, Waldenstrom's macroglobulinemia, among others. It is a Bruton's tyrosine kinase inhibitor that acts on B-cell receptor signaling pathway and predisposes to various infections due to its effects on neutrophils, monocytes and T cells. We present a case of cerebral invasive aspergillosis in a patient being treated with ibrutinib for relapsed chronic lymphocytic leukemia. It was hard to associate the condition to ibrutinib versus the chronic lymphocytic leukemia. The patient was successfully treated with a combination of voriconazole and micafungin, resulting in complete recovery and no residual deficits. This highlights the importance of recognizing the rare complication in those on ibrutinib and initiating the treatment immediately with appropriate antifungal agents to improve prognosis of this potentially fatal condition.
Selective delivery of therapeutic agents into solid tumors has been a major challenge impeding the achievement of long-term disease remission and cure. The need to develop alternative drug delivery routes to achieve higher drug concentration in tumor tissue, reduce unwanted off-target side effects and thus achieve greater therapeutic efficacy, has resulted in an explosive body of research. Bifidobacterium spp. are anaerobic, nonpathogenic, Gram-positive bacteria, commensal to the human gut that are a possible anticancer drug-delivery vehicle. In this review, we describe Bifidobacterium's microbiology, current clinical applications, overview of the preclinical work investigating Bifidobacterium's potential to deliver anticancer therapy, and review the different strategies used up to date. Finally, we discuss both current challenges and future prospects.
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