Harald Stein, MD, PhDa and Volker Diehl, MD, PhDb∗,     aBerlin Reference and Consultation Center for Lymphoma and Hematopathology, Pathodiagnostik Berlin, Komturstrasse 58-62, Berlin 12099, Germany; bClinic I for Internal Medicine, University of Cologne, 50937 Köln, Joseph Stelzmannstr, Germany

∗Corresponding author.

Hodgkin’s disease (HD) is a fatal disorder with the unique histologic features of few dysplastic Hodgkin- and Reed-Sternberg (HRS) cells surrounded by an abundance of nonatypical bystander cells in primary biopsies. By using the first Hodgkin cell line L428 the cytokine receptor CD30 was discovered. CD30 proved to be an excellent target for the diagnoses of CD30+ malignancies and for monoclonal antibody therapy in patients with these malignancies because of its highly restricted expression in healthy individuals. Recently, a new anti-CD30-toxin-drug-conjugate consisting of an anti-CD30 monoclonal antibody bound to the nonimmunogenic toxin auristatin E with a newly designed linker was generated.

Keywords

Hodgkin lymphoma

Establishment of the cell line L428

Detection of the CD30 Antigen

Key points

Why was it essential to establish a Hodgkin cell line?

When the histology of Hodgkin disease (HD) was investigated (1898 first by Sternberg1 and 4 years later by Reed2), an unusual cellular composition for a fatal disorder was observed (Fig. 1). Most of the cells in the affected lymph nodes proved to be nonatypical bystander cells (ie, lymphocytes, plasma cells, histiocytes, neutrophilic and/or eosinophilic granulocytes, and others). The atypical large mononuclear and multinuclear blastoid cells, called Hodgkin and Reed-Sternberg (HRS) cells, were found in the minority, ranging from 0.1% to 1% of all cells present in the specimen.3 Because of this, it was thought that HD is more likely an infectious disease or an inflammatory process than a true neoplasm. The rarity of the HRS cells and the abundance of surrounding bystander cells made the investigation of HRS cells with special techniques impossible.

The establishment of the L428 cell line

To obtain pure HRS cells in large quantities, many laboratories tried to establish long-term in vitro cultures of primary HRS cells when in the 1960s and 1970s suitable culture conditions like RPMI media together with fetal calf serum became available. All attempts by Zech and colleagues,4 Kaplan and Gartner,5 and many others were unsuccessful. The same was true for the 427 culture attempts by Volker Diehl and his group between 1969 and 1978 at the Radiumhemmet/Karolinska Sjukhuset in Stockholm/Sweden and later in Hannover/Germany. Most of the culture attempts resulted in Epstein-Barr virus-transformed lymphoblastoid cell cultures. After his relocation to Hannover, Diehl continued with the attempts to establish in vitro cultures of Hodgkin-Reed-Sternberg cells and succeeded with his team in 1979 in growing for the first time a permanently growing Epstein-Barr virus-negative cell line from a pleural effusion of a young female patient with nodular sclerosing HD (Table 1).6,7

Discovery of the CD30 antigen and its application in research, diagnostic, and therapy