Cetuximab, a monoclonal antibody targeting the epidermal growth factor receptor (EGFR), is associated with various adverse reactions, among which skin-related adverse events (AEs) are common. This case report details a patient who developed severe skin AEs after cetuximab administration and outlines a reproducible management protocol. The patient, a 44-year-old man with KRAS wild-type metastatic rectal cancer, was undergoing cetuximab-based chemotherapy. Approximately 10 days after initiating a cetuximab monotherapy cycle following prior combination regimens, he developed severe Grade 3-4 acneiform rash and erythema multiforme-like lesions with ulceration, exudation, crusting, scaling, and hyperpigmentation on the face and anterior chest. Evaluation included physical examination, dermatology consultation, skin biopsy for histopathology and direct immunofluorescence, and laboratory tests (including serum IgE, eosinophil count, C-reactive protein, HLA-A*31:01 genotyping, viral serologies, and bacterial cultures). Management involved permanent discontinuation of cetuximab, high-dose intravenous methylprednisolone (1.5 mg∙kg∙day), cyclosporine (3 mg∙kg∙day), supportive wound care in a burn unit, and topical ocular/oral care. Symptoms improved significantly within 72 h, with a 90% reduction in lesion severity by day 14. Therapy was successfully transitioned to bevacizumab plus FOLFOX after dermatologic recovery, with no rash recurrence during follow-up. This case highlights the importance of early recognition, multidisciplinary management, and protocol-driven intervention for severe cetuximab-induced skin toxicity to ensure patient safety and treatment continuity.
The widely used rotavirus (RV) vaccine, Rotateq, contained reassortment strains of human and bovine G1/2/3/4P[5] RVs. The functional and structural features of bovine G1P[5] VP8* were investigated. Bovine G1P[5] VP8* was identified to interact with sialic acids and sialic acid-containing glycans. In addition, P[5] VP8* recognized α-Gal histo-blood group antigens (HBGAs). Bovine G1P[5] VP8* did not hemagglutinate the tested red blood cells. The crystal structure of P[5] VP8* was determined at 1.7 Å. Structural superimposition revealed that P[5] VP8* was most close to human P[8] VP8*, while much further to VP8*s of porcine P[7] and rhesus P[3]. Sequence alignment showed that amino acids of the putative glycan binding site in P[5] VP8* were different to those in P[3]/P[7] VP8*s, indicating that P[5] VP8* may interact with glycans using different mechanism. This study provided more understanding of P[5] RV infection and the interactions of RV VP8* and glycans.
Refractory B-cell lymphomas are difficult to successfully treat with current chemotherapeutic regimens; however, immunotherapy may be an effective form of treatment for these patients. Fourteen refractory lymphoma patients (age, 29-74 y) were enrolled in the trial. α-1,3-galactosyl (α-Gal) epitopes were synthesized on lymphoma cell membranes with the use of bovine recombinant α-1,3-galactosyltransferase (α-GT) and neuraminidase to enhance tumor immunogenicity. Subsequent incubation of processed cell membranes with autologous dendritic cells (DCs) in the presence of human serum containing abundant natural anti-α-Gal immunoglobulin G led to the effective phagocytosis of tumor membranes by DCs. The pulsed DCs and autologous cytokine-induced killer cells were then co-cultured to promote maximum cytotoxicity to lymphoma cells and were infused back into the donor lymphoma patients. Therapeutic responses were assessed by clinical observation, laboratory tests and a computed tomography scan at 6 months after treatment. Complete and partial remission occurred in four and three patients, respectively. The disease status remained unchanged in five patients, and disease progression was observed in two patients. No serious side effects or autoimmune diseases were observed in any participants. Serum lactate dehydrogenase and β2-macroglobulin decreased in 11 and 14 patients, respectively. All patients showed robust systemic cytotoxicity in response to tumor lysate as measured by interferon-γ expression in peripheral blood mononuclear cells after treatment (P < 0.001). The number of peripheral immune effector cells (CD3(+)/CD4(+), CD8(+)/CD28(+) and CD16(+)/CD56(+) cells) increased significantly (P < 0.05) 3 months after treatment. Lymphoma cell-specific α-Gal immunotherapy is safe, effective and has great potential for the treatment of refractory B-cell lymphoma.
To evaluate the safety and clinical efficacy of a new immunotherapy using both α-Gal epitope-pulsed dendritic cells (DCs) and cytokine-induced killer cells. Freshly collected hepatocellular carcinoma (HCC) tumor tissues were incubated with a mixture of neuraminidase and recombinant α1,3-galactosyltransferase (α1,3GT) to synthesize α-Gal epitopes on carbohydrate chains of the glycoproteins of tumor membranes. The subsequent incubation of the processed membranes in the presence of human natural anti-Gal IgG resulted in the effective phagocytosis to the tumor membrane by DCs. Eighteen patients aged 38-78 years with stage III primary HCC were randomLy chosen for the study; 9 patients served as controls, and 9 patients were enrolled in the study group. The evaluation demonstrated that the procedure was safe; no serious side effects or autoimmune diseases were observed. The therapy significantly prolonged the survival of treated patients as compared with the controls (17.1 ± 2.01 mo vs 10.1 ± 4.5 mo, P = 0.00121). After treatment, all patients in the study group had positive delayed hypersensitivity and robust systemic cytotoxicity in response to tumor lysate as measured by interferon-γ-expression in peripheral blood mononuclear cells using enzyme-linked immunosorbent spot assay. They also displayed increased numbers of CD8-, CD45RO- and CD56-positive cells in the peripheral blood and decreased α-fetoprotein level in the serum. This new tumor-specific immunotherapy is safe, effective and has a great potential for the treatment of tumors.