Enhanced T-lymphocyte infiltration in a desmoid tumor of the thoracic wall in a young woman treated with intratumoral injections of the oncolytic peptide LTX-315: a case report

Abstract

Background: Desmoid tumors are intermediary malignant, fibrous lesions occurring in various soft tissues. Surgical treatment is relentlessly challenging because of the propensity for local aggressive behavior and high risk of recurrence. Consequently, a wide range of oncological drugs and radiation therapy are being used; however, outcomes are unpredictable. We investigated whether local treatment with an oncolytic peptide could be beneficial in a patient with an unresectable desmoid tumor.

Case presentation: In a young 29-year-old Caucasian woman who was diagnosed with a retromammary desmoid tumor infiltrating deeply into the anterior thoracic wall, surgery was considered excessively mutilating, and observation was recommended. The lesion progressed, however, and caused debilitating pain, despite nonsteroidal anti-inflammatory medication. Subcutaneous injections of human interferon-α (Multiferon®) resulted in reduced growth kinetics but had to be terminated because of development of symptomatic pneumonitis. Frequently used oncological treatment was withheld because of the toxicity profile, and the patient was instead included in a phase I study investigating transdermal intratumoral injection of LTX-315, an oncolytic peptide that induces anticancer immune responses ( ClinicalTrials.gov , NCT01986426 ). A marked increase of CD8+ tumor-infiltrating T cells in the lesion was complemented by upregulation of immune gene signature (including effector T-cell, T-helper type 1 cell, chemokine, and cytokine genes). These changes were followed by gradual symptom relief and long-term disease stabilization, indicating clinical benefit. LTX-315 was well tolerated until termination in week 16 after a serious allergic reaction.

Conclusions: Our patient was treated with repeated intratumoral injections of LTX-315, resulting in tumor regression accompanied by upregulation of immune genes and T-cell infiltration. Local application of immunotherapy, minimizing systemic side effects, represents a novel treatment modality in desmoid tumors that should be tested in further clinical trials.

Keywords: Desmoid tumors; Immune gene expression profiles; Intratumoral oncolytic peptide; T-cell infiltration.

Conflict of interest statement

HP and ØR are employees of Lytix Biopharma. All of the other coauthors and the first author declare that they have no competing personal or political interests, commercial associations, or financial interests.

Figures

Fig. 1

This diagram has been provided to the author by Lytix Biopharma and approved for use in this article by medical chief officer as well as co-founder of Lytix Biopharma

Fig. 2

LTX-315 mode of action

Fig. 3

Radiological evaluation. Magnetic resonance imaging (t1 weighted) demonstrating frontal (a, b) (yellow arrows indicating cranial tumour border) and axial (c, d) (yellow arrows indicating medial tumour border) sections of pretreatment (a, c) and follow-up (b, d) examination 19 months after completion of intratumoural LTX-315 injections

Fig. 4

Pre- and post-treatment biopsies. Haemotoxylin and Eosin staining and staining of CD3+ and CD8+ T cells in pretreatment biopsy (left column), postinduction week 7 (middle column), and at the end of treatment 18 weeks later (right column)

Fig. 5

T-cell analyses. a Graph showing the abundance of unique T-cell clones in blood (peripheral blood mononuclear cells) before treatment compared with 7 weeks after initiation of LTX-315 treatment. T-cell clones that were not significantly changed in frequency are depicted in gray, whereas those that were significantly expanding or contracting are depicted in red or blue, respectively. Dashed diagonal gray line defines frequency equality, and dashed red line defines threshold for statistical comparison. b Trivariate analysis of T-cell clones in blood (similar analysis to that in a) compared with the T-cell clones in the tumor after LTX-315 treatment. T-cell clones colored without transparency and with a black peripheral line were also present in the tumor tissue

Fig. 6

Gene expression profiles. LTX-315 induced upregulation of key genes involved in tumor regression and transformed the gene expression from cold (blue) to hot (red). Hierarchical clustering of Immunosign 21 immune gene signature (HalioDx) profiling a predefined set of effector T-cell, T-helper type 1 cell, chemokine, and cytokine genes