Background and Aims

Our laboratory has previously studied human, polyclonal, Natural Antibodies (NAbs) endowed with polyreactivity and cell-penetrating capacity in Intravenous Immunoglobulin therapeutic preparations. Recently, our interest has been focused on human monoclonal IgGs (mIgGs) endowed with Cell-Penetrating ability (CPAbs). In particular, we aimed to analyze CPAbs potential anti-neoplastic biological activities in metastatic breast cancer cells.

Methods

A series of mIgGs from Multiple Myeloma-G patients sera (known to contain high concentration of mIgGs exhibiting frequently NAb-like properties) were isolated by protein-G chromatography. The purity and monoclonality of mIgGs were verified by SDS-PAGE and IEF, respectively, while their polyreactivity against self- and non-self- antigens, by ELISA. mIgGs cell-penetrating capacity was analyzed in MDA-MB-231 metastatic breast cancer cells by immunofluorescence experiments and their effect on apoptosis and cancer cell migration, by flow cytometry and wound healing assays, respectively.

Results

Among 41 purified human mIgGs, 19 had cell-penetrating capacity with distinct cytoplasmic staining patterns. Three CPAbs inhibited MDA-MB-231 cell migration and also induced apoptosis. Moreover, two other CPAbs, which enhanced MDA-MB-231 motility, had no effect on their viability likewise to four CPAbs and three mIgGs without cell-penetrating capacity which also had no effect nor on cellular migration or cell viability.

Conclusions

We provide evidence that human natural mIgGs with cell-penetrating capacity exhibit anti-neoplastic functions and could be exploited as advantageous -due to their natural origin- anti-neoplastic tools. In conclusion, we consider that CPAbs could be used in cancer immunotherapy either per se, or as carriers for intracellular drug delivery, or both.

Background and Aims

We report on a 66 years old female patient with systemic sclerosis (first diagnosed in year 2016 with limited skin sclerosis, anti-Scl-70-antibody, raynaud symptoms) who developed metastatic parotiscarcinoma (lung, lymph nodes) in march 2019 and was introduced to chemotherapy with paclitaxel.

Methods

After four cycles of therapy with paclitaxel, CT-scan showed regression of lung metastases. At the same time, massive progression of systemic sclerosis with diffuse skin sclerosis and new manifestations like digital ulcers, dysphagia with oesophageal hypomotility, lung fibrosis and pulmonal arterial hypertension occurred. Moreover, the patient developed leuco- and thrombocytopenia due to chemotherapy.

Results

Since several cases of induction of scleroderma-like skin lesions during the therapy with paclitaxel were described in the literature, chemotherapy with paclitaxel was paused after consultation of an oncologist. We started prednisolone (10 mg daily) and mycophenolate-mofetil (1 g daily) in order to improve lung fibrosis and skin sclerosis which were the most prominent manifestations of systemic sclerosis in our patient. Unfortunately, the patient could not take mycophenolate-mofetil because of dysphagia and burning in the mouth. Currently we are planning to start extracorporeal photopheresis as well as therapy with nintedanib.

Conclusions

Management of patients with autoimmune and metastatic tumour diseases demands interdisciplinary exchange, for which we suggest autoimmune board meetings (including dermatologists, cardiologists, oncologists, pulmonologists, pathologists, rheumatologists and radiologists).

Background and Aims

Vasculitis as a paraneoplasic syndrome is rare and the pathofiosology is yet unclear. Association between ANCA vasculitis and solid tumour is an even rarer condition with very few cases in literature.

Methods

73 year old woman admitted for vision loss with migraine headache, weight loss, asthenia and low fever. She had diabetes, arterial hypertension, prothrombin gene mutation and aortic and mitral valve biological prosthesis. Ophthalmology suggested isquemic optic neuropathy and was referred to internal Medicine.

Results

She was anaemic, high erythrocyte sedimentation rate, positive rheumatoid factor with normal complement and negative HIV and hepatitis. Doppler of the temporal, facial and occipital arteries showed a thickness without halo and biopsy was absent for giant cells. Serologies were positive for C-ANCA antibodies with anti-PR3 of 361. Methylprednisolone was given with partial recuperation of sight. Biopsy of nose turbinate and CT scan of sinus and thorax where absent for granuloma. The patient responded well lowering the erythrocyte sedimentation rate and continued improvement of sight but without lowering of C-ANCA title, 621 at a second evaluation. After discharge was readmitted for myocardial infarction this admission was complicated by endocarditis to streptococcus oralis and hematochezia. Colonoscopy revealed adenocarcinoma and underwent hemicolectomy with adenectomy after undergoing 2 cycles of chemotherapy and suspending all steroids there was no evidence of vasculitis with a lowering of the antibody title to 300.

Conclusions

The authors present a case of a tumor induced vasculitis whose diagnosis precedes that of the tumor and whose symptoms and antibody titer improve only with tumor control and treatment.

Background and Aims

Anti-DFS70/LEDGFp75 auto-antibodies (Anti-DFS 70 Ab) usually target the dense fine speckled protein of 70kDa (DFS70), commonly known as lens epithelium-derived growth factor p75 (LEDGFp75).

This auto-antigen is thought to be a stress response protein that is ubiquitously expressed in mammalian cells and tissues, with overexpression in cancer cells and tumors such as breast cancer

The aim of our work was to study the frequency of Anti-DFS70 Ab and if they could be a new biomarker in breast cancer.

Methods

Is a prospective descriptive study including 32 patients with a breast cancer in Military Hospital of Tunis

The blood samples and clinical data were collected from all patients. The Serological analyses were performed using Dot Technic EUROIMMUN ^© in the laboratory of immunology. Written informed consent was obtained from all participants

Results

The middle age of patients was 47 years

We found a frequency of 15,63 % of Anti-DFS70 Ab in our breast cancer patients

There was a significant correlation between Anti DFS 70 Ab and the tumor size (p=0.038 <p=0.5).

We have noted also that all patients with lymph node involvement have positive Anti- DFS70 Ab.

Conclusions

Our results suggests that Anti-DFS Ab could be a new biomarker in breast cancer.

A more large study is needed to confirm our results.

Background and Aims

Although immune checkpoint inhibitors (ICI) have revolutionized cancer therapy, their use is associated with immune toxicities referred to as immune-related adverse events (irAE). Here we describe the clinical presentation and management of rheumatic immune-related adverse events (Rh-irAE) in a national multi-center cohort.

Methods

All patients presenting with Rh-irAE at 9 academic sites across Canada between January 2013 and January 2019 were identified and included in this retrospective cohort study. Standardized data were extracted by chart review.

Results

117 patients who developed 136 Rh-irAE were identified. The most frequent Rh-irAE was symmetric polyarthritis (n=45). Other Rh-irAE included non-inflammatory musculoskeletal symptoms (n=18), polymyalgia rheumatica (n=17) and myositis (n=9).

Prednisone was the most commonly used treatment (n=76) with a mean maximum dose of 60 ± 74 mg/d and duration of treatment of 8.4 ± 11 months. Forty-two patients required conventional synthetic disease-modifying anti-rheumatic drugs (DMARD) and two required biologic DMARD to control the Rh-irAE. ICI was discontinued due to the Rh-irAE in 22 patients. There were no deaths related to Rh-irAE.

Treatment of the Rh-irAE did not appear to negatively impact the tumor response to immunotherapy with 23 patients experiencing tumor progression prior to treatment of the Rh-irAE and 13 following treatment.

Conclusions

In this largest multi-center cohort of Rh-irAE described to-date, symmetric polyarthritis was the most common Rh-irAE. There was considerable heterogeneity of treatment, although this did not appear to negatively impact the anti-tumor response. This study can inform the development of evidence-based recommendations to optimize Rh-irAE and cancer outcomes in patients treated with ICI.

Background and Aims

Patients with autoimmune disorders (AD) have altered cancer risks compared to the general population. Systemic lupus erythematosus and multiple sclerosis lead to a heightened risk for hematological malignancies and decreased risk for breast, ovarian, and prostate malignancies. Often patients with autoimmune disease have dysregulated antiviral immune responses, including against oncogenic viruses.

Methods

We extracted electronic health records (EHR) from Vanderbilt University. ICD-9/10 codes and laboratory values were collected for hematological, lung, anal-vaginal, thyroid, hepatobiliary, bladder, prostate, and breast cancers; and viruses including Epstein Barr virus (EBV), Herpesviruses (HPV), and Hepatitis A/B/C (Hep). Only viral infections that led to a physician visit or laboratory test were entered into the EMR; therefore, only clinically relevant cases were noted and considered positive in this study. The relationship between virus infection and cancer in an SLE cohort (SLE-cases n=2,313, and SLE-controls n=5,702) and an MS cohort (MS-case n=7,277, MS-control n=7,277) was examined by multilinear logistic regression.

Results

Viral infection was strongly associated with increased risk for cancer overall. SLE and MS patients were more susceptible to all viral infections. MS patients trended toward increased risk for cancers overall, while decreased risk for hormone-based cancers in SLE patients non-significantly reduced their risk for overall cancer. Both SLE and MS patients had increased clinically relevant EBV infection, which was associated with risk for hematological cancers.

Conclusions

Viral Infection is assoicate with malignacy in two autoimmune diseases. Preventing viral infections by vaccination may be especially helpful in controlling risk for cancer in SLE and MS patients

Background and Aims

At the moment, there are no predictive markers of immune adverse events (IAE), which makes timely diagnosis very difficult. In 2011 criteria for determining Autoimmune-Inflammatory syndrome induced by adjuvants (ASIA) were proposed (Y. Shoenfeld, 2011). This study aims to identify the clinical manifestations of ASIA, as well as to determine the extent to which the influence of trigger factors listed in the “ASIA Questionnaire” are significant.

Methods

We examined patients (n=50) being treated for solid tumors at St. Petersburg City Clinical Oncology Center. Among the patients, 30 took nivolumab, 15-pembrolizumab, and 5-combined immunotherapy. To assess the impact of exogenous and endogenous trigger factors, all patients were interviewed using the “ASIA” standardized questionnaire. Supported by Grant (contract № 14.W03.31.0009 13.02.2017).

Results

The signs of ASIA syndrome were found in 72 % (36/50) of patients. The most frequent clinical manifestations were arthralgia-33% (12/36) and rash - 28% (10/36). The development of thyroiditis was detected in 8% (3/36) of cases, and hepatitis in 6% (2/36). No relationship was found between the development of ASIA and the influence of trigger factors, the previous presence of ASIA symptoms, and the type of drug used.

Conclusions

Our results exceed the frequency of complications according to the literature data, which may be due to a more extensive list of analyzed criteria and subjective assessment of the patient's condition. Development of specific complications corresponds to the results of past studies. It was shown that studied ICI induce ASIA symptoms regardless previous clinical symptoms of autoimmune processes and different types of trigger affection.